Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Lung Metabolism of Eicosanoids: Prostaglandins, Prostacyclin, Thromboxane, and Leukotrienes

Y. S. Bakhle, Sergio H. Ferreira

10.1002/cphy.cp030111

Source: Supplement 10: Handbook of Physiology, The Respiratory System, Circulation and Nonrespiratory Functions

Originally published: 1985

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 History of Eicosanoids
2 Overview of Eicosanoid Biosynthesis
3 Antagonists of Eicosanoids and Inhibitors of Their Synthesis
4 Lung Pharmacology of Eicosanoids
5 Inactivation of Eicosanoids in Lung
6 Synthesis of Eicosanoids by Lung
6.1 Synthesis From Exogenous Arachidonic Acid
6.2 Synthesis From Endogenous Arachidonic Acid
7 Summary
Figure 1. Figure 1.

Synthetic pathway of cyclooxygenase products.
Figure 2. Figure 2.

Synthetic pathway of lipoxygenase products.


Figure 1.

Synthetic pathway of cyclooxygenase products.



Figure 2.

Synthetic pathway of lipoxygenase products.

References
 1. Adcock, J. J., and L. G. Garland. A possible role for lipoxygenase products as regulators of airway smooth muscle reactivity. Br. J. Pharmacol. 69: 167–169, 1980.
 2. Alabaster, V. A. Inactivation of endogenous amines in the lungs. In: Lung Biology in Health and Disease. Metabolic Functions of the Lung, edited by Y. S. Bakhle and J. R. Vane. New York: Dekker, 1977, vol. 4, p. 3–31.
 3. Alabaster, V. A. Metabolism of arachidonic acid and its endoperoxide prostaglandin H2 in isolated lungs from guinea pigs and rabbits (Abstract). J. Physiol. London 293: 28P, 1979.
 4. Alabaster, V. A. Metabolism of arachidonic acid and its endoperoxide (PGH2) to myotropic products in guinea‐pig and rabbit isolated lungs. Br. J. Pharmacol. 69: 479–489, 1980.
 5. Alabaster, V. A., and Y. S. Bakhle. Release of smooth muscle contracting substances from isolated perfused lungs. Eur. J. Pharmacol. 35: 349–360, 1976.
 6. Ali, A. E., J. C. Barrett, and T. E. Eling. Prostaglandin and thromboxane production by fibroblasts and vascular endothelial cells. Prostaglandins 20: 667–688, 1980.
 7. Al‐Ubaidi, F., and Y. S. Bakhle. What is the fate of exogenous prostaglandin endoperoxide, PGH2, in isolated lung (Abstract)? J. Physiol. London 293: 20P, 1979.
 8. Al‐Ubaidi, F., and Y. S. Bakhle. The fate of exogenous arachidonic acid in guinea‐pig isolated lungs. J. Physiol London 295: 445–455, 1979.
 9. Al‐Ubaidi, F., and Y. S. Bakhle. Differences in biological activation of arachidonic acid in perfused lungs from guinea pig, rat and man. Eur. J. Pharmacol. 62: 89–96, 1980.
 10. Al‐Ubaidi, F., and Y. S. Bakhle. Metabolism of 14C‐arachi‐donate in rat isolated lung. Prostaglandins 19: 747–759, 1980.
 11. Al‐Ubaidi, F., and Y. S. Bakhle. Metabolism of vasoactive hormones in human isolated lung. Clin. Sci. 58: 45–51, 1980.
 12. Anderson, F. L., W. Jubiz, T. J. Tsagaris, and H. Kuida. Endotoxin‐induced prostaglandin E and F release in dogs. Am. J. Physiol. 228: 410–414, 1975.
 13. Anderson, M. W., and T. E. Eling. Prostaglandin removal and metabolism by isolated perfused rat lung. Prostaglandins 11: 645–677, 1976.
 14. Änggård, E., C. Larsson, and B. Samuelsson. The distribution of 15‐hydroxy prostaglandin dehydrogenase and prostaglandin‐Δ13‐reductase in tissues of the swine. Acta Physiol. Scand. 81: 396–404, 1971.
 15. Änggård, E., and B. Samuelsson. Prostaglandins and related factors. 28. Metabolism of prostaglandin E1 in guinea pig lung: the structures of two metabolites. J. Biol. Chem. 239: 4097–4102, 1964.
 16. Änggård, E., and B. Samuelsson. Prostaglandins and related factors. 38. Biosynthesis of prostaglandins from arachidonic acid in guinea pig lung. J. Biol. Chem. 240: 3518–3521, 1965.
 17. Änggård, E., and B. Samuelsson. Purification and properties of a 15‐hydroxyprostaglandin dehydrogenase from swine lung. Ark. Kemi. 25: 293–300, 1966.
 18. Armstrong, J. M., A. L. A. Boura, M. Hamberg, and B. Samuelsson. A comparison of the vasodepressor effects of the cyclic endoperoxides PGG2 and PGH2 with those of PGD2 and PGE2 in hypertensive and normotensive rats. Eur. J. Pharmacol. 39: 251–258, 1976.
 19. Armstrong, J. M., N. Lattimer, S. Moncada, and J. R. Vane. Comparison of the vasodepressor effects of prostacyclin and 6‐oxo‐prostaglandin F1α with those of prostaglandin E2 in rats and rabbits. Br. J. Pharmacol. 62: 125–130, 1978.
 20. Augstein, J., J. B. Farmer, T. B. Lee, P. Sheard, and M. L. Tattersall. Selective inhibitor of slow reacting substance of anaphylaxis. Nature London New Biol. 245: 215–217, 1973.
 21. Bach, M. K., and J. R. Brashler. In vivo and in vitro production of a slow reacting substance in the rat upon treatment with calcium ionophores. J. Immunol. 113: 2040–2044, 1974.
 22. Bach, M. K., J. R. Brashler, M. A. Johnson, and J. M. Drazen. Two rat mononuclear cell‐derived slow reacting substances: kinetic evidence that the peripheral airways‐selective spasmogen is derived from a nonselectively acting precursor. Immunopharmacology 2: 361–373, 1980.
 23. Bakhle, Y. S. Action of prostaglandin dehydrogenase inhibitors on prostaglandin uptake in rat isolated lung. Br. J. Pharmacol. 65: 635–639, 1979.
 24. Bakhle, Y. S. Biosynthesis of prostaglandins and thromboxanes in lung. Bull. Eur. Physiopathol. Respir. 17: 491–508, 1981.
 25. Bakhle, Y. S. Inhibition by clinically used dyes of prostaglandin inactivation in rat and human lung. Br. J. Pharmacol. 72: 715–722, 1981.
 26. Bakhle, Y. S., and A. J. Block. Effects of halothane on pulmonary inactivation of noradrenaline and prostaglandin E2 in anaesthetized dogs. Clin. Sci. Mol. Med. 50: 87–90, 1976.
 27. Bakhle, Y. S., J. Hartiala, H. Toivonen, and P. Uotila. Effects of cigarette smoke on the metabolism of vasoactive hormones in rat isolated lungs. Br. J. Pharmacol. 65: 495–500, 1979.
 28. Bakhle, Y. S., S. Jancar, and B. J. R. Whittle. Uptake and inactivation of prostaglandin E2 methyl analogues in the rat pulmonary circulation. Br. J. Pharmacol. 62: 275–280, 1978.
 29. Bakhle, Y. S., and T. W. Smith. Release of spasmogens from rat isolated lungs by tryptamines. Eur. J. Pharmacol. 46: 31–39, 1977.
 30. Bakhle, Y. S., and J. T. Zakrzewski. Effects of the oestrous cycle on the metabolism of arachidonic acid in rat isolated lung. J. Physiol. London 326: 411–423, 1982.
 31. Bakhle, Y. S., and J. T. Zakrzewski. Inactivation of prostaglandin E2 by rat isolated lung during the oestrous cycle. J. Endocrinol. 98: 47–53, 1983.
 32. Bedwani, J. R., and P. B. Marley. Enhanced inactivation of prostaglandin E2 by the rabbit during pregnancy or progesterone treatment. Br. J. Pharmacol. 53: 547–554, 1979.
 33. Ben‐Harari, R. R., and M. B. H. Youdim. Ontogenesis of uptake and deamination of 5‐hydroxytryptamine, dopamine and β‐phenylethylamine in isolated perfused lung and lung homogenates from rats. Br. J. Pharmacol. 72: 731–737, 1981.
 34. Benzie, R., J. R. Boot, and W. Dawson. A preliminary investigation of prostaglandin synthetase activity in normal, sensitized and challenged sensitized guinea‐pig lung (Abstract). J. Physiol. London 246: 80P–81P, 1975.
 35. Bergström, S., and B. Samuelsson. The prostaglandins. Endeavour 23: 109–113, 1968.
 36. Berry, E. M., J. F. Edmonds, and J. H. Wyllie. Release of prostaglandin E2 and unidentified factors from ventilated lungs. Br. J. Surg. 58: 189–192, 1971.
 37. Berti, F., G. C. Folco, A. Giachetti, S. Malandrino, C. Omini, and T. Vigano. Atropine inhibits thromboxane A2 generation in isolated lungs of the guinea pig. Br. J. Pharmacol. 68: 467–472, 1980.
 38. Berti, F., G. C. Folco, S. Nicosia, C. Omini, and R. Pasargiklian. The role of histamine H1‐ and H2‐receptors in the generation of thromboxane A2 in perfused guinea‐pig lungs. Br. J. Pharmacol. 65: 629–633, 1979.
 39. Berti, F., G. C. Folco, and C. Omini. Pharmacological control of thromboxane A2 in lung. Bull. Eur. Physiopathol. Respir. 17: 509–552, 1981.
 40. Bito, L. Z., R. A. Baroody, and M. E. Reitz. Dependence of pulmonary prostaglandin metabolism on carrier‐mediated transport processes. Am. J. Physiol. 232 (Endocrinol. Metab. Gastrointest. Physiol. 1): E382–E387, 1977.
 41. Blackwell, G. J., R. Carnuccio, M. Di Rosa, R. J. Flower, L. Parente, and P. Persico. Macrocortin: a polypeptide causing the anti‐phospholipase effect of glucocorticoids. Nature London 287: 147–149, 1980.
 42. Blackwell, G. J., and R. J. Flower. Effects of steroid hormones on tissue levels of prostaglandin 15‐hydroxydehy‐drogenase in the rat (Abstract). Br. J. Pharmacol. 56: 343P–344P, 1976.
 43. Blackwell, G. J., and R. J. Flower. Glucocorticoids, lungs and prostaglandins. Bull. Eur. Physiopathol. Respir. 17: 595–607, 1981.
 44. Blackwell, G. J., R. J. Flower, F. P. Nijkamp, and J. R. Vane. Phospholipase A2 activity of guinea‐pig isolated perfused lungs: stimulation, and inhibition by anti‐inflammatory steroids. Br. J. Pharmacol. 62: 79–89, 1978.
 45. Blackwell, G. J., R. J. Flower, N. Russell‐Smith, J. A. Salmon, P. B. Thorogood, and J. R. Vane. 1‐n‐Butylimidazole: a potent and selective inhibitor of “thromboxane synthetase” (Abstract). Br. J. Pharmacol. 64: 435P, 1978.
 46. Blair, I. A., S. E. Barrow, K. A. Waddell, P. J. Lewis, and C. T. Dollery. Prostacyclin is not a circulating hormone in man. Prostaglandins 23: 579–589, 1982.
 47. Bø, G., J. Hognestad, and J. Vaage. The role of blood platelets in pulmonary responses to microembolization with barium sulphate. Acta Physiol. Scand. 90: 244–251, 1974.
 48. Boot, J. R., A. F. Cockerill, W. Dawson, D. N. Mallen, and D. J. Osborne. Modification of prostaglandin and thromboxane release by immunological sensitization and successive immunological challenges from guinea‐pig lungs. Int. Arch. Allergy Appl. Immunol. 57: 159–164, 1978.
 49. Borgeat, P., and B. Samuelsson. Arachidonic acid metabolism in polymorphonuclear leukocytes: unstable intermediate in formation of dihydroxy acids. Proc. Natl. Acad. Sci. USA 76: 3213–3217, 1979.
 50. Boura, A. L. A., and R. D. Murphy. Some factors affecting inactivation of prostaglandin E2 (PGE2) by the rat isolated perfused lung (Abstract). Br. J. Pharmacol. 62: 411P, 1978.
 51. Brigham, K. L., and M. L. Ogletree. Effects of prostaglandins and related compounds on lung vascular permeability. Bull. Eur. Physiopathol. Respir. 17: 703–722, 1981.
 52. Brocklehurst, W. E. The release of histamine and formation of a slow‐reacting substance (SRS‐A) during anaphylactic shock. J. Physiol. London 151: 416–435, 1960.
 53. Bunting, S., S. Moncada, J. R. Vane, H. F. Woods, and M. J. Weston. Prostacyclin improves hemocompatibility during charcoal hemoperfusion. In: Prostacyclin, edited by S. Bergström and J. R. Vane. New York: Raven, 1979, p. 361–369.
 54. Burka, J. F., and R. J. Flower. Effects of modulators of arachidonic acid metabolism on the synthesis and release of slow‐reacting substance of anaphylaxis. Br. J. Pharmacol. 65: 35–41, 1979.
 55. Cedro, A., and K. Herbaczyńska‐Cedro. Increased blood level of prostaglandin‐like substances during cardiopulmonary bypass in the dog. Cardiovasc. Res. 12: 516–522, 1978.
 56. Chaudhari, A., K. Sivarajah, R. Warwick, T. E. Eling, and M. W. Anderson. Inhibition of pulmonary prostaglandin metabolism by exposure of animals to oxygen or nitrogen dioxide. Biochem. J. 184: 51–57, 1979.
 57. Chignard, M., A. Prancan, J. Lefort, F. Dray, and B. B. Vargaftig. Arachidonate‐mediated bronchoconstriction and platelet activation are inhibited by microgram doses of compound L8027 which are not selective for thromboxane synthetase. Agents Actions 4, Suppl.: 184–187, 1979.
 58. Chignard, M., and B. B. Vargaftig. Dog platelets fail to aggregate when they form aggregating substances upon stimulation with arachidonic acid. Eur. J. Pharmacol. 38: 7–18, 1976.
 59. Clegg, P. C., W. J. Hall, and V. R. Pickles. The action of ketonic prostaglandins on the guinea‐pig myometrium. J. Physiol. London 183: 123–144, 1966.
 60. Cockerill, A. F., D. N. B. Mallen, D. J. Osborne, J. R. Boot, and W. Dawson. The identification of two novel prostaglandins and a thromboxane. Prostaglandins 13: 1033–1042, 1977.
 61. Cohen, G. M., P. Uotila, J. Hartiala, E. M. Suolinna, N. Simberg, and O. Pelkonen. Metabolism and covalent binding of [3H]benzo(a)pyrene by isolated perfused lungs and short‐term tracheal organ culture of cigarette smoke‐exposed rats. Cancer Res. 37: 2147–2155, 1977.
 62. Collier, H. O. J. New light on how aspirin works. Nature London 223: 35–37, 1969.
 63. Collier, H. O. J., and P. J. Gardiner. Prostaglandin receptors in the airways. In: Metabolic Activities of the Lung, edited by R. Porter and J. Whelan Amsterdam: Excerpta Med., 1980, p. 333–350. (Ciba Found. Symp. 78.)
 64. Collier, H. O. J., and G. W. L. James. Humoral factors affecting pulmonary inflation during acute anaphylaxis in the guinea‐pig in vivo. Br. J. Pharmacol. 30: 283–301, 1967.
 65. Collier, H. O. J., and W. J. F. Sweatman. Antagonism by fenamates of prostaglandin F2α and of slow reacting substance on human bronchial muscle. Nature London 219: 864–865, 1968.
 66. Crutchley, D. J., J. A. Boyd, and T. E. Eling. Enhanced thromboxane B2 release from challenged guinea pig lung after oxygen exposure. Am. Rev. Respir. Dis. 121: 695–699, 1980.
 67. Crutchley, D. J., and P. J. Piper. Inhibition of the pulmonary inactivation of prostaglandins in vivo by di‐4‐phloretin phosphate. Br. J. Pharmacol. 54: 301–307, 1975.
 68. Cuthbert, M. F. Prostaglandins and asthma. Br. J. Clin. Pharmacol. 2: 293–295, 1975.
 69. Dahlén, S. E., P. Hedqvist, S. Hammarström, and B. Samuelsson. Leukotrienes are potent constrictors of human bronchi. Nature London 288: 484–486, 1980.
 70. D'Angelo, V., S. Villa, M. Mysliwiec, M. B. Donati, and G. de Gaetano. Defective fibrinolytic and prostacyclin‐like activity in human atheromatous plaques. Thromb. Diath. Haemorrh. 39: 535–536, 1978.
 71. Danon, A., and G. Assouline. Inhibition of prostaglandin biosynthesis by corticosteroids requires RNA and protein synthesis. Nature London 273: 552–554, 1978.
 72. Dawson, C. A., B. O. Cozzini, and A. J. Lonigro. Metabolism of [2‐14C]prostaglandin E1 on passage through the pulmonary circulation. Can. J. Physiol. Pharmacol. 53: 610–615, 1975.
 73. Dawson, W., J. R. Boot, A. F. Cockerill, D. N. B. Mallen, and D. J. Osborne. Release of novel prostaglandins and thromboxanes after immunological challenge of guinea pig lung. Nature London 262: 699–702, 1976.
 74. Dawson, W., J. R. Boot, E. A. Kitchen, and J. R. Walker. Inhibition of lipoxygenase related effector systems. In: SRS‐A and Leukotrienes, edited by P. J. Piper. New York: Wiley, 1981, p. 219–226.
 75. Di Rosa, M., and P. Persico. Latency and reversion of hydrocortisone inhibition of prostaglandin biosynthesis in rat leucocytes. In: Arachidonic Acid Metabolism: Proc. Eur. Workshop on Inflammation, 1st, Basel, edited by K. Brune and M. Baggiolini Basel: Springer‐Verlag, 1979, p. 63–68.
 76. Drazen, J. M., R. A. Lewis, S. I. Wasserman, R. P. Orange, and K. F. Austen. Differential effects of a partially purified preparation of slow‐reacting substance of anaphylaxis on guinea pig tracheal spirals and parenchymal strips. J. Clin. Invest. 63: 1–5, 1979.
 77. Ducharme, D. W., J. R. Weeks, and R. G. Montgomery. Studies on the mechanism of the hypertensive effect of prostaglandin F2α. J. Pharmacol. Exp. Ther. 160: 1–10, 1968.
 78. Dusting, G. J., S. Moncada, and J. R. Vane. Recirculation of prostacyclin PGI2 in the dog. Br. J. Pharmacol. 64: 315–320, 1978.
 79. Edlund, A., W. Bonfim, L. Kaijser, C. Olin, C. Patrono, E. Pinca, and W. Wennmalm. Pulmonary formation of prostacyclin in man. Prostaglandins 22: 323–332, 1981.
 80. Egerton‐Vernon, J. M., and J. R. Bedwani. Prostaglandin 15‐hydroxydehydrogenase activity during pregnancy in rabbits and rats. Eur. J. Pharmacol. 33: 405–408, 1975.
 81. Eling, T. E., H. J. Hawkins, and M. W. Anderson. Structural requirements for, and the effects of chemicals on, the rat pulmonary inactivation of prostaglandins. Prostaglandins 14: 51–60, 1977.
 82. Engineer, D. M., U. Niederhauser, P. J. Piper, and P. Sirois. Release of mediators of anaphylaxis: inhibition of prostaglandin synthesis and the modification of the release of slow‐reacting substance of anaphylaxis and histamine. Br. J. Pharmacol. 62: 61–66, 1978.
 83. Feldberg, W., and C. H. Kellaway. Liberation of histamine and formation of lysolecithin‐like substances by cobra venom. J. Physiol. London 94: 187–226, 1938.
 84. Ferreira, S. H. Prostaglandins. In: Chemical Messengers of the Inflammatory Process, edited by J. C. Houck. Amsterdam: North‐Holland, 1979, p. 113–151.
 85. Ferreira, S. H., and Y. S. Bakhle. Inactivation of bradykinin and related peptides in the lungs. In: Lung Biology in Health and Disease. Metabolic Functions of the Lung, edited by Y. S. Bakhle and J. R. Vane. New York: Dekker, 1977, vol. 4, p. 35–53.
 86. Ferreira, S. H., L. J. Greene, M. C. O. Salgado, and E. M. Krieger. The fate of circulating biologically active peptides in the lungs. In: Metabolic Activities of the Lungs, edited by R. Porter and J. Whelan Amsterdam: Excerpta Med., 1980, p. 129–140. (Ciba Found. Symp. 78.)
 87. Ferreira, S. H., S. Moncada, and J. R. Vane. Indomethacin and aspirin abolish prostaglandin release from the spleen. Nature London New Biol. 231: 237–239, 1971.
 88. Ferreira, S. H., and J. R. Vane. Prostaglandins: their disappearance from and release into the circulation. Nature London 216: 868–873, 1967.
 89. Ferreira, S. H., and J. R. Vane. Mode of action of antiinflammatory agents which are prostaglandin synthetase inhibitors. In: Handbook of Experimental Pharmacology. Anti‐Inflammatory Drugs, edited by J. R. Vane and S. H. Ferreira. Berlin: Springer‐Verlag, 1979, vol. 50, pt. 2, p. 348–398.
 90. Fishburne, J. T., W. F. Brenner, J. T. Braksma, and C. H. Hendricks. Bronchospasm complicating intravenous prostaglandin F2α for therapeutic abortion. Obstet. Gynecol. 39: 892–898, 1972.
 91. Fishman, A. P. Hypoxia on the pulmonary circulation. Circ. Res. 38: 221–231, 1976.
 92. Fletcher, J. R., and P. W. Ramwell. Altered lung metabolism of prostaglandins during hemorrhagic and endotoxin shock. Surg. Forum 28: 184–186, 1977.
 93. Fletcher, J. R., and P. W. Ramwell. Modification by aspirin and indomethacin of the haemodynamic and prostaglandin releasing effects of E. coli endotoxin in the dog. Br. J. Pharmacol. 61: 175–181, 1977.
 94. Fletcher, J. R., and P. W. Ramwell. Modulation of prostaglandins E and F by the lung in baboon hemorrhagic shock. J. Surg. Res. 26: 465–472, 1979.
 95. Floman, Y., N. Floman, and U. Zor. Inhibition of prostaglandin E release by anti‐inflammatory steroids. Prostaglandins 11: 591–594, 1976.
 96. Flower, R. J. Drugs which inhibit prostaglandin biosynthesis. Pharmacol. Rev. 26: 33–67, 1974.
 97. Flower, R. J. Prostaglandins and related compounds. In: Handbook of Experimental Pharmacology. Anti‐Inflammatory Drugs, edited by J. R. Vane and S. H. Ferreira. Berlin: Springer‐Verlag, 1979, vol. 50, pt. 2, p. 373–415.
 98. Flower, R. J. Steroidal anti‐inflammatory drugs as inhibitors of phospholipase A2. Adv. Prostaglandin Thromboxane Res. 3: 105–112, 1978.
 99. Flower, R. J., and J. R. Vane. Inhibition of prostaglandin synthetase in brain explains the anti‐pyretic activity of paracetamol (4‐acetamidophenol). Nature London 240: 410–411, 1972.
 100. Ford‐Hutchinson, A. W., M. A. Bray, F. M. Cunningham, E. M. Davidson, and M. J. H. Smith. Isomers of leukotriene B4 possess different biological potencies. Prostaglandins 21: 143–152, 1981.
 101. Ford‐Hutchinson, A. W., M. A. Bray, M. V. Doig, M. E. Shipley, and M. J. H. Smith. Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature London 286: 264–265, 1980.
 102. Fountain, S. W., B. A. Martin, C. E. Musclow, and J. D. Cooper. Pulmonary leukostasis and its relationship to pulmonary dysfunction in sheep and rabbits. Circ. Res. 46: 175–180, 1980.
 103. Frey, H.‐H., and C. Dengjel. Antagonism of arachidonic acid‐induced bronchoconstriction in cats by aspirin‐like analgesics. Eur. J. Pharmacol. 40: 345–348, 1976.
 104. Friedman, L. S., T. M. Fitzpatrick, P. W. Ramwell, and P. A. Kot. Thromboxane B2 inhibits the pulmonary metabolism of PGE2 in the anesthetized dog. Adv. Prostaglandin Thromboxane Res. 7: 981–983, 1980.
 105. Gardiner, P. J., and H. O. J. Collier. Specific receptors for prostaglandins in airways. Prostaglandins 19: 819–841, 1980.
 106. Gardiner, P. J., J. L. Copas, C. Schneider, and H. O. J. Collier. 2‐Decarboxy‐2‐hydroxymethyl prostaglandin E1 (TR4161), a prostaglandin bronchodilator of low tracheobronchial irritancy. Prostaglandins 19: 349–370, 1980.
 107. Gilmore, N., J. R. Vane, and J. H. Wyllie. Prostaglandins released by the spleen. Nature London 218: 1135–1140, 1968.
 108. Gilmore, N., J. R. Vane, and J. H. Wyllie. Prostaglandin release by the spleen in response to an infusion of particles. In: Prostaglandins, Peptides and Amines, edited by P. Mantegazza and E. W. Horton. London: Academic, 1969, p. 21–29.
 109. Goldblatt, M. W. Properties of human seminal fluid. J. Physiol London 84: 208–218, 1935.
 110. Gorman, R. R., G. L. Bundy, D. C. Peterson, F. F. Sun, O. V. Miller, and F. A. Fitzpatrick. Inhibition of human platelet thromboxane synthetase by 9,11‐azoprosta‐5,13‐dienoic acid. Proc. Natl. Acad. Sci. USA 74: 4007–4011, 1977.
 111. Greenway, C. V., and V. S. Murthy. Mesenteric vasoconstriction after endotoxin administration in cats pretreated with aspirin. Br. J. Pharmacol. 43: 259–269, 1971.
 112. Greig, M. E., and R. L. Griffin. Antagonism of slow reacting substance in anaphylaxis (SRS‐A) and other spasmogens on the guinea pig tracheal chain by hydrotropic acids and their effects on anaphylaxis. J. Med. Chem. 18: 112–116, 1975.
 113. Griffith, O. W., and A. Meister. Translocation of intracellular glutathione to membrane‐bound γ‐glutamyl transpeptidase as a discrete step in the γ‐glutamyl cycle: glutathionuria after inhibition of transpeptidase. Proc. Natl. Acad. Sci. USA 76: 268–272, 1979.
 114. Gryglewski, R. J. Prostacyclin as a circulating hormone. Biochem. Pharmacol. 28: 2161–2166, 1979.
 115. Gryglewski, R. J., A. Dembinska‐Kiec, L. Grodzinska, and B. Panczenko. Differential generation of substances with prostaglandin‐like and thromboxane‐like activities by guinea pig trachea and lung strips. In: Lung Cells in Disease, edited by A. Bouhuys Amsterdam: North‐Holland, 1976, p. 289–307.
 116. Gryglewski, R. J., R. Korbut, and A. C. Ocetkiewicz. Generation of prostacyclin by lungs in vivo and its release into the arterial circulation. Nature London 273: 765–767, 1978.
 117. Gryglewski, R. J., B. Panczenko, R. Korbut, L. Grodzinska, and A. Ocetkiewicz. Corticosteroids inhibit prostaglandin release from perfused mesenteric blood vessels of rabbit and from perfused lungs of sensitized guinea pig. Prostaglandins 10: 343–355, 1975.
 118. Gryglewski, R. J., and J. R. Vane. The release of prostaglandins and rabbit aorta contracting substance (RCS) from rabbit spleen and its antagonism by anti‐inflammatory drugs. Br. J. Pharmacol. 45: 37–47, 1972.
 119. Hagedorn, B., and H. B. Kostenbauder. Studies on the effect of tobacco smoke on the biotransformation of vasoactive substances in the isolated perfused rabbit lung. I. Prostaglandin F2α. Res. Commun. Chem. Pathol. Pharmacol. 18: 495–506, 1977.
 120. Hamberg, M., P. Hedqvist, K. Strandberg, J. Svensson, and B. Samuelsson. Prostaglandin endoperoxides. IV. Effects on smooth muscle. Life Sci. 16: 451–462, 1975.
 121. Hamberg, M., and B. Samuelsson. Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis. Proc. Natl. Acad. Sci. USA 70: 899–903, 1973.
 122. Hamberg, M., and B. Samuelsson. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc. Natl. Acad. Sci. USA 71: 3400–3404, 1974.
 123. Hamberg, M., J. Svensson, P. Hedqvist, K. Strandberg, and B. Samuelsson. Involvement of endoperoxides and thromboxanes in anaphylactic reactions. Adv. Prostaglandin Thromboxane Res. 1: 495–501, 1976.
 124. Hamberg, M., J. Svensson, and B. Samuelsson. Thromboxanes, a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Natl. Acad. Sci. USA 71: 345–349, 1975.
 125. Hammerschmidt, D. E., L. J. Weaver, L. D. Hudson, P. R. Craddock, and H. S. Jacob. Association of complement activation and elevated plasma C5a with adult respiratory distress syndrome. Lancet 1: 947–949, 1980.
 126. Hammond, G. L., L. Cronau, D. Whittaker, and C. N. Gillis. Fate of prostaglandins E1 and A1 in the human pulmonary circulation. Surgery 81: 716–722, 1977.
 127. Hansen, H. S. 15‐Hydroxyprostaglandin dehydrogenase. A review. Prostaglandins 12: 647–679, 1976.
 128. Hansen, H. S. Purification and characterization of a 15‐ketoprostaglandin Δ13‐reductase from bovine lung. Biochim. Biophys. Acta 574: 136–145, 1979.
 129. Hartiala, J., P. Uotila, and T. W. Nienstedt. The effects of cigarette smoke exposure on testosterone metabolism in the isolated perfused rat lung. J. Steroid Biochem. 9: 365–368, 1978.
 130. Haslam, R. J., and M. D. McClenaghan. Measurement of circulating prostacyclin. Nature London 292: 364–366, 1981.
 131. Hauge, A., P. K. M. Lunde, and B. A. Waaler. Effects of prostaglandin E1 and adrenaline on the pulmonary vascular resistance (PVR) in isolated rabbit lungs. Life Sci. 6: 673–680, 1967.
 132. Hawkins, H. J., J. B. Smith, K. C. Nicolaou, and T. E. Eling. Studies of the mechanism involved in the fate of prostacyclin (PGI2) and 6‐keto‐PGF1α in the pulmonary circulation. Prostaglandins 16: 871–884, 1978.
 133. Hedqvist, P., S. E. Dahlen, L. Gustafsson, S. Hammarström, and B. Samuelsson. Biological profile of leukotrienes C4 and D4. Acta Physiol. Scand. 110: 331–333, 1980.
 134. Hedqvist, P., A. Holmgren, and A. A. Mathé. Effect of prostaglandin F2α on airway resistance in man (Abstract). Acta Physiol. Scand. 82: 29A, 1971.
 135. Hemker, D. P., R. J. Shebuski, and J. W. Aiken. Release of a prostacyclin‐like substance into the circulation of dogs by intravenous adenosine diphosphate. J. Pharmacol. Exp. Ther. 212: 246–252, 1980.
 136. Hemler, M. E., and W. E. M. Lands. Evidence for a peroxide‐initiated free radical mechanism of prostaglandin biosynthesis. J. Biol. Chem. 255: 6253–6261, 1980.
 137. Hensby, C. N., P. J. Barnes, C. T. Dollery, and H. Dargie. Production of 6‐oxo‐PGF1α by human lung in vivo. Lancet 2: 1162–1163, 1979.
 138. Higgs, G. A., and R. J. Flower. Anti‐inflammatory drugs and the inhibition of arachidonate lipoxygenase. In: SRS‐A and Leukotrienes, edited by P. J. Piper. New York: Wiley, 1981, p. 197–207.
 139. Hitchcock, M. Effect of inhibitors of prostaglandin synthesis and prostaglandins E2 and F2α on the immunologic release of mediators of inflammation from actively sensitized guinea‐pig lung. J. Pharmacol. Exp. Ther. 207: 630–640, 1978.
 140. Horton, E. W., and R. L. Jones. Prostaglandins A1, A2 and 19‐hydroxy A1; their actions on smooth muscle and their inactivation on passage through the pulmonary and hepatic portal vascular beds. Br. J. Pharmacol. 37: 705–722, 1969.
 141. Horton, E. W., and R. L. Jones. Biological activity of prostaglandin D2 on smooth muscle (Abstract). Br. J. Pharmacol. 52: 110P–111P, 1974.
 142. Hoult, J. R. S., and P. K. Moore. Effects of sulphasalazine and its metabolites on prostaglandin synthesis, inactivation and actions on smooth muscle. Br. J. Pharmacol. 68: 719–730, 1980.
 143. Hyman, A. L. The active responses of pulmonary veins in intact dogs to prostaglandins F2α and E1. J. Pharmacol. Exp. Ther. 165: 267–273, 1969.
 144. Hyman, A. L., A. A. Mathé, C. A. Leslie, C. C. Matthews, J. T. Bennett, E. W. Spannhake, and P. J. Kadowitz. Modification of pulmonary vascular responses to arachidonic acid by alterations in physiologic state. J. Pharmacol. Exp. Ther. 207: 388–401, 1978.
 145. Hyman, A. L., E. W. Spannhake, and P. J. Kadowitz. Prostaglandins and the lung. Am. Rev. Respir. Dis. 117: 111–136, 1978.
 146. Johnson, R. A., D. R. Morton, J. H. Vinner, R. R. Gorman, J. C. McGuire, F. F. Sun, N. Whittaker, S. Bunting, J. A. Salmon, S. Moncada, and J. R. Vane. The chemical structure of prostaglandin X (prostacyclin). Prostaglandins 12: 915–928, 1976.
 147. Jose, P. J., U. Niederhauser, P. J. Piper, C. Robinson, and A. P. Smith. Degradation of prostaglandin F2α in the human pulmonary circulation. Thorax 31: 713–719, 1976.
 148. Jose, P. J., and J. P. Seale. Incorporation and metabolism of [14C]‐arachidonic acid in guinea‐pig lungs. Br. J. Pharmacol. 67: 519–526, 1979.
 149. Junod, A. F., and C. Ody. Amine uptake and metabolism by endothelium of pig pulmonary artery and aorta. Am. J. Physiol. 232 (Cell Physiol. 1): C88–C94, 1977.
 150. Kadowitz, P. J., B. M. Chapnick, L. P. Feigen, A. L. Hyman, P. K. Nelson, and E. W. Spannhake. Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin, PGI2. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 45: 408–413, 1978.
 151. Kadowitz, P. J., C. A. Gruetter, D. B. McNamara, R. R. Gorman, E. W. Spannhake, and A. L. Hyman. Comparative effects of endoperoxide PGH2 and an analog on the pulmonary vascular bed. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42: 953–958, 1977.
 152. Kadowitz, P. J., and A. L. Hyman. Influence of a prostaglandin endoperoxide analogue on the canine pulmonary vascular bed. Circ. Res. 40: 282–287, 1977.
 153. Kadowitz, P. J., D. B. McNamara, H. S. She, E. W. Spannhake, and A. L. Hyman. Arachidonic acid responses in the lung. Bull. Eur. Physiopathol. Respir. 17: 659–674, 1981.
 154. Karim, S. M. M., P. G. Adaikan, and S. R. Kottegoda. Prostaglandins and human respiratory tract smooth muscle: structure activity relationship. Adv. Prostaglandin Thromboxane Res. 7: 969–980, 1980.
 155. Kellaway, C. H., and E. R. Trethewie. The liberation of a slow reacting smooth muscle‐stimulating substance in anaphylaxis. Q. J. Exp. Physiol. 30: 121–145, 1940.
 156. Kistler, G. S., P. R. B. Caldwell, and E. R. Weibel. Development of fine structural damage to alveolar and capillary lining cells in oxygen‐poisoned rat lungs. J. Cell Biol. 32: 605–628, 1967.
 157. Klein, L. S., A. B. Fisher, S. Soltoff, and R. F. Colburn. Effect of oxygen exposure on pulmonary metabolism of prostaglandin E2. Am. Rev. Respir. Dis. 118: 622–625, 1978.
 158. Kokobu, T., E. Ueda, K. Nishimura, and N. Yoshida. Angiotensin I converting enzyme activity in pulmonary tissue of fetal and newborn rabbits. Experientia 33: 1137–1138, 1977.
 159. Ku, E. C., and J. M. Wasvary. Inhibition of prostaglandin synthetase by Su‐21524 (Abstract). Federation Proc. 32: 3302, 1973.
 160. Kuehl, F. A., Jr., J. L. Humes, E. A. Ham, R. W. Egan, and H. W. Dougherty. Inflammation: the role of peroxidasederived products. Adv. Prostaglandin Thromboxane Res. 6: 77–86, 1980.
 161. Lambley, J. E., and A. P. Smith. The effects of arachidonic acid, indomethacin and SC‐19220 on guinea‐pig tracheal muscle tone. Eur. J. Pharmacol. 30: 148–153, 1975.
 162. Lands, W. E. M., P. R. Letellier, L. H. Rome, and J. Y. Vanderhoek. Modes of inhibiting the prostaglandin biosynthesis. In: Advances in the Biosciences, edited by S. Bergström and S. Bernhard New York: Pergamon, 1973, vol. 9, p. 15–28.
 163. Large, B. J., P. F. Leswell, and P. R. Maxwell. Bronchodilator activity of prostaglandin E1 in experimental animals. Nature London 224: 78–80, 1969.
 164. Larsson, C., and E. Änggård. Distribution of prostaglandin metabolizing enzymes in tissues of the swine. Acta Pharmacol. Toxicol. Suppl. 28: 61, 1970.
 165. Lauersen, N. H., and K. H. Wilson. The role of a long‐acting vaginal suppository of 15‐ME‐PGB2α in first and second trimester abortion. Adv. Prostaglandin Thromboxane Res. 8: 1435–1441, 1980.
 166. Leary, W. P., A. C. Asmal, and J. Botha. Pulmonary inactivation of prostaglandins by hypertensive rats. Prostaglandins 13: 697–700, 1977.
 167. Lee, S. C., and L. Levine. Purification and properties of chicken heart prostaglandin Δ13‐reductase. Biochem. Biophys. Res. Commun. 61: 14–21, 1974.
 168. Leffler, C.W., and J. R. Hessler. Pulmonary and systemic vascular effect of exogenous prostaglandin I2 in fetal lambs. Eur. J. Pharmacol. 54: 37–42, 1979.
 169. Leffler, C. W., T. L. Tyler, and S. Cassin. Effect of indomethacin on pulmonary vascular response to ventilation of fetal goats. Am. J. Physiol. 234 (Heart Circ. Physiol. 3): H346–H351, 1978.
 170. Lefort, J., and B. B. Vargaftig. Role of platelets in aspirinsensitive bronchoconstriction in the guinea‐pig; interactions with salicylic acid. Br. J. Pharmacol. 63: 35–42, 1978.
 171. Leslie, C. A., and L. Levine. Evidence for the presence of a prostaglandin E2‐9‐keto reductase in rat organs. Biochem. Biophys. Res. Commun. 52: 717–724, 1973.
 172. Lewis, P., and H. M. Tyler (editors). Clinical prospects for a thromboxane synthetase inhibitor. Br. J. Clin. Pharmacol. 15, Suppl. 1: 5S–139S, 1983.
 173. Lewis, R. A., K. F. Austen, J. M. Drazen, D. A. Clark, A. Marfat, and E. J. Corey. Slow reacting substances of anaphylaxis: identification of leukotrienes C‐1 and D from human and rat sources. Proc. Natl. Acad. Sci. USA 77: 3710–3714, 1980.
 174. Lewis, R. A., J. M. Drazen, K. F. Austen, D. A. Clark, and E. J. Corey. Identification of the C(6)‐S conjugate to leukotriene A with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS‐A). Importance of the 11‐cis‐geometry for biological activity. Biochem. Biophys. Res. Commun. 96: 271–277, 1980.
 175. Liebig, R., W. Bernauer, and B. A. Peskar. Release of prostaglandins, a prostaglandin metabolite, slow reacting substance and histamine from anaphylactic lungs and its modification by catecholamines. Naunyn‐Schmiedebergs Arch. Pharmakol. 284: 279–293, 1974.
 176. Lindsey, H. E., and J. H. Wyllie. Release of prostaglandins from embolized lungs. Br. J. Surg. 57: 738–741, 1970.
 177. Longmore, D. B., G. Bennett, D. Gueirrara, M. Smith, S. Bunting, S. Moncada, P. Reed, N. G. Read, and J. R. Vane. Prostacyclin: a solution to some problems of extracorporeal circulation. Experiments in greyhounds. Lancet 1: 1002–1005, 1979.
 178. Lulich, K. M., H. W. Mitchell, and M. P. Sparrow. The cat lung strip as an in vitro preparation of peripheral airways: a comparison of β‐adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea. Br. J. Pharmacol. 58: 71–79, 1976.
 179. Magerlein, B. J., D. W. Ducharme, W. E. Magee, W. L. Miller, A. Robert, and J. R. Weeks. Synthesis and biological properties of 16‐alkylprostaglandins. Prostaglandins 4: 143–145, 1973.
 180. Maggi, F. M., N. Tyrrell, Y. Maddox, W. Watkins, E. R. Ramey, and P. W. Ramwell. Prostaglandin synthetase activity in vascular tissue of male and female rats. Prostaglandins 19: 985–993, 1980.
 181. Main, I. H. M. The inhibitory actions of prostaglandins on respiratory smooth muscle. Br. J. Pharmacol. 22: 511–519, 1964.
 182. Männistö, J., and P. Uotila. Cigarette smoke ventilation decreases prostaglandin inactivation in rat and hamster lungs. Prostaglandins 23: 833–839, 1982.
 183. Marrazzi, M. A., J. E. Shaw, F. T. Tao, and F. M. Matchinsky. Reversibility of 15‐hydroxyprostaglandin dehydrogenase from swine lung. Prostaglandins 1: 389–395, 1972.
 184. Massion, W. H., B. Rosenbluth, and M. Kux. Protective effect of methyl prednisolone against lung complications in endotoxin shock. South. Med. J. 65: 941–944, 1972.
 185. Mathé, A. A., P. Hedqvist, A. Holmgren, and N. Svanborg. Bronchial hyperreactivity to prostaglandin F2α and histamine in patients with asthma. Br. Med. J. 1: 193–196, 1973.
 186. Mathé, A. A., and L. Levine. Release of prostaglandins and metabolites from guinea‐pig lung: inhibition by catecholamines. Prostaglandins 4: 877–890, 1973.
 187. McGiff, J. C., N. A. Terragno, J. C. Strand, J. B. Lee, and A. J. Lonigro. Selective passage of prostaglandins across the lung. Nature London 223: 742–745, 1969.
 188. McGuire, J. C., and F. F. Sun. Metabolism of prostacyclin. Oxidation by rhesus monkey lung 15‐hydroxyl prostaglandin dehydrogenase. Arch. Biochem. Biophys. 189: 92–96, 1978.
 189. Mitchell, H. W., and M. A. Denborough. Anaphylaxis in guinea‐pig peripheral airways in vitro. Eur. J. Pharmacol. 54: 69–78, 1979.
 190. Moncada, S., S. Bunting, K. M. Mullane, P. Thorogood, J. R. Vane, A. Raz, and P. Needleman. A selective potent antagonist of thromboxane synthetase. Prostaglandins 13: 611–618, 1977.
 191. Moncada, S., R. J. Gryglewski, S. Bunting, and J. R. Vane. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature London 263: 663–665, 1976.
 192. Moncada, S., R. J. Gryglewski, S. Bunting, and J. R. Vane. A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation. Prostaglandins 12: 715–737, 1976.
 193. Moncada, S., A. G. Herman, E. A. Higgs, and J. R. Vane. Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for the anti‐thrombotic properties of vascular endothelium. Thromb. Res. 11: 323–344, 1977.
 194. Moncada, S., R. Korbut, S. Bunting, and J. R. Vane. Prostacyclin is a circulating hormone. Nature London 273: 767–768, 1978.
 195. Moncada, S., P. Needleman, S. Bunting, and J. R. Vane. Prostaglandin endoperoxide and thromboxane generating systems and their selective inhibition. Prostaglandins 12: 323–325, 1976.
 196. Moncada, S., and J. R. Vane. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2 and prostacyclin. Pharmacol. Rev. 30: 293–331, 1979.
 197. Morris, H. R., P. J. Piper, G. W. Taylor, and J. R. Tippins. The role of arachidonate lipoxygenase in the release of SRS‐A from guinea‐pig chopped lung. Prostaglandins 19: 371–383, 1980.
 198. Morris, H. R., G. W. Taylor, P. J. Piper, M. N. Samhoun, and J. R. Tippins. Slow reacting substances (SRSs); the structure identification of SRSs from rat basophil leukaemia (RBL‐1) cells. Prostaglandins 19: 185–201, 1980.
 199. Morris, H. R., G. W. Taylor, P. J. Piper, and J. R. Tippins. Structure of slow reacting substance of anaphylaxis from guinea‐pig lung. Nature London 285: 104–106, 1980.
 200. Morse, H. C., III, K. J. Bloch, and K. F. Austen. Biologic properties of rat antibodies. II. Time‐course of appearance of antibodies involved in antigen‐induced release of slow reacting substance of anaphylaxis (SRS‐A rat); association of the activity with rat IgGa. J. Immunol. 101: 658–663, 1968.
 201. Mullane, K. M., G. J. Dusting, J. A. Salmon, S. Moncada, and J. R. Vane. Biotransformation and cardiovascular effects of arachidonic acid in the dog. Eur. J. Pharmacol. 54: 217–228, 1979.
 202. Murao, M., K. Uchiyama, A. Shida, K. Sakai, T. Yusa, and T. Yamoguchi. Studies on 20‐isopropylidene PGE2 as a new aerosol bronchodilator. Adv. Prostaglandin Thromboxane Res. 7: 985–988, 1980.
 203. Murphy, R. C., S. Hammarström, and B. Samuelsson. Leukotriene C: a slow reacting substance from murine mastocytoma cells. Proc. Natl. Acad. Sci. USA 76: 4275–4279, 1979.
 204. Nakano, J., and R. B. McCloy, Jr. Effects of indomethacin on the pulmonary vascular and airway resistance responses to pulmonary microembolization. Proc. Soc. Exp. Biol. Med. 143: 218–221, 1973.
 205. Nakano, J., and N. Y. Morsy. Beta oxidation of prostaglandins E1 and E2 in rat lung and kidney homogenates (Abstract). Clin. Res. 19: 142, 1971.
 206. Nakano, J., and A. V. Prancan. Metabolic degradation of prostaglandin E1 in lung and kidney of rats in endotoxin shock. Proc. Soc. Exp. Biol. Med. 144: 506–508, 1973.
 207. Needleman, P. Experimental criteria for evaluating prostaglandin biosynthesis and intrinsic function. Biochem. Pharmacol. 27: 1515–1518, 1978.
 208. Needleman, P., M. S. Minkes, and J. R. Douglas. Stimulation of prostaglandin biosynthesis by adenine nucleotides. Profile of prostaglandin release by perfused organs. Circ. Res. 34: 455–460, 1974.
 209. Nijkamp, F. P., S. Moncada, H. L. White, and J. R. Vane. Diversion of prostaglandin endoperoxide metabolism by selective inhibition of thromboxane A2 biosynthesis in lung, spleen or platelets. Eur. J. Pharmacol. 44: 179–187, 1977.
 210. Nijkamp, F. P., and A. G. M. Ramakers. Prevention of anaphylactic bronchoconstriction by a lipoxygenase inhibitor. Eur. J. Pharmacol. 62: 121–122, 1980.
 211. Nugteren, D. H. Inhibition of prostaglandin biosynthesis by 8cis, 12trans, 14cis‐eicosatrienoic acid and 5cis, 8cis, 12trans, 14cis‐eicosatetraenoic acid. Biochim. Biophys. Acta 210: 171–176, 1970.
 212. Nugteren, D. H. Arachidonate lipoxygenase in blood platelets. Biochim. Biophys. Acta 380: 299–307, 1975.
 213. Nugteren, D. H., and E. Hazelhof. Isolation and properties of intermediates in prostaglandin biosynthesis. Biochim. Biophys. Acta 326: 448–461, 1973.
 214. Ody, C., Y. Dieterle, I. Wand, H. Stalder, and A. F. Junod. PGA1 and PGF2α metabolism by pig pulmonary endothelium, smooth muscle, and fibroblasts. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 46: 211–216, 1979.
 215. Olley, P. M., F. Coceani, and G. Kent. Inactivation of prostaglandin E1 by lungs of the foetal lamb. Experientia 30: 58–59, 1974.
 216. Onishi, H., H. Kosuzume, Y. Kitamura, K. Yamaguchi, M. Nobuhara, Y. Suzuki, S. Yoshida, H. Tomioka, and A. Kumagai. Structure of slow‐reacting substance of anaphylaxis (SRS‐A). Prostaglandins 20: 655–667, 1980.
 217. Orange, R. P., D. J. Stechschulte, and K. F. Austen. Immunochemical and biologic properties of rat IgE. II. Capacity to mediate the immunologic release of histamine and slow reacting substance of anaphylaxis (SRS‐A). J. Immunol. 105: 1087–1095, 1970.
 218. Pace‐Asciak, C. R. Biosynthesis and metabolism of prostaglandin during animal development. Adv. Prostaglandin Thromboxane Res. 1: 35–46, 1976.
 219. Pace‐Asciak, C., and D. Miller. Prostaglandins during development. Age‐dependent activity profiles of prostaglandin 15‐hydroxydehydrogenase and 13, 14‐reductase in lung tissue from late prenatal, early postnatal and adult rats. Prostaglandins 4: 351–362, 1973.
 220. Palmer, M. A., P. J. Piper, and J. R. Vane. Release of rabbit aorta contracting substance (RCS) and prostaglandins induced by chemical or mechanical stimulation of guinea‐pig lungs. Br. J. Pharmacol. 49: 226–242, 1973.
 221. Palmer, R. J., R. Stepney, G. A. Higgs, and K. E. Eakins. Chemokinetic activity of arachidonic acid lipoxygenase products on leukocytes from different species. Prostaglandins 20: 411–418, 1980.
 222. Parkes, D. P., and T. E. Eling. The influence of environmental agents on prostaglandin biosynthesis and metabolism by the lung. Biochem. J. 146: 549–556, 1975.
 223. Patel, K., and Y. S. Bakhle. Thromboxane B2 (TxB2) metabolism in rat isolated lung and its inhibition by drugs. Prostaglandins Med. 10: 221–229, 1983.
 224. Paterson, N. A. M., J. F. Burka, and I. D. Craig. Release of slow‐reacting substance of anaphylaxis from dispersed pig lung cells: effects of cyclooxygenase and lipoxygenase inhibitors. J. Allergy Clin. Immunol. 67: 426–434, 1981.
 225. Patterson, R., and K. E. Harris. Inhibition of immunoglobulin E‐mediated, antigen‐induced monkey asthma and skin reactions by 5, 8, 11, 14‐eicosatetraynoic acid. J. Allergy Clin. Immunol. 67: 146–152, 1981.
 226. Patterson, R., J. J. Pruzansky, and K. E. Harris. An agent that releases basophil and mast cell histamine but blocks cyclooxygenase and lipoxygenase metabolism of arachidonic acid inhibits immunoglobulin E‐mediated asthma in rhesus monkeys. J. Allergy Clin. Immunol. 67: 444–449, 1981.
 227. Pavek, K., P. J. Piper, and G. Smedegård. Anaphylatoxin‐induced shock and two patterns of anaphylactic shock: hemodynamics and mediators. Acta Physiol. Scand. 105: 393–403, 1979.
 228. Piper, P. J. (editor). SRS‐A and the Leukotrienes. New York: Wiley, 1981.
 229. Piper, P. J., and M. N. Samhoun. The mechanism of action of leukotrienes C4 and D4 in guinea‐pig isolated perfused lung and parenchymal strips of guinea pig, rabbit and rat. Prostaglandins 21: 793–803, 1981.
 230. Piper, P. J., M. N. Samhoun, J. R. Tippins, T. J. Williams, M. A. Palmer, and M. J. Peck. Pharmacological studies on pure SRS‐A and synthetic leukotrienes C4 and D4. In: SRS‐A and Leukotrienes, edited by P. J. Piper. New York: Wiley, 1981, p. 81–99.
 231. Piper, P. J., and D. M. Temple. The effect of lipoxygenase inhibitors and diethylcarbamazine on the immunological release of slow reacting substance of anaphylaxis (SRS‐A) from guinea‐pig chopped lung. J. Pharm. Pharmacol. 33: 384–386, 1981.
 232. Piper, P. J., J. R. Tippins, M. N. Samhoun, H. R. Morris, G. W. Taylor, and C. M. Jones. SRS‐A and its formation by the lung. Bull. Eur. Physiopathol. Respir. 17: 571–586, 1981.
 233. Piper, P. J., and J. R. Vane. Release of additional factors in anaphylaxis and its antagonism by anti‐inflammatory drugs. Nature London 223: 29–35, 1969.
 234. Piper, P. J., and J. R. Vane. The release of prostaglandin from lung and other tissues. Ann. NY Acad. Sci. 180: 363–385, 1971.
 235. Piper, P. J., J. R. Vane, and J. H. Wyllie. Inactivation of prostaglandins by the lungs. Nature London 225: 600–604, 1970.
 236. Pitt, B. R., C. N. Gillis, and G. L. Hammond. Influence of the lung on arterial levels of endogenous prostaglandins E and F. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 50: 1161–1167, 1981.
 237. Platshon, L. F., and M. Kaliner. The effects of the immunological release of histamine upon human lung cyclic nucleotide levels and prostaglandin generation. J. Clin. Invest. 62: 1113–1121, 1978.
 238. Powell, W. S. Omega‐oxidation of prostaglandins by lung and liver microsomes. Changes in enzyme activity induced by pregnancy, pseudopregnancy, and progesterone. J. Biol. Chem. 253: 6711–6716, 1978.
 239. Powell, W. S., and S. Solomon. Formation of 20‐hydroxyprostaglandins by lungs of pregnant rabbits. J. Biol. Chem. 253: 4609–4616, 1978.
 240. Poyser, N. L. Prostaglandins in Reproduction. New York: Wiley, 1981, chapt. 9, p. 238–242.
 241. Prancan, A. V., J. Lefort, M. Chignard, K. Gerozissis, F. Dray, and B. B. Vargaftig. L8027 and 1‐nonyl‐imidazole as non‐selective inhibitors of thromboxane synthesis. Eur. J. Pharmacol. 60: 287–297, 1979.
 242. Robinson, C., S. H. Peers, K. A. Waddell, I. A. Blair, and J. R. S. Hoult. Thromboxane B2 uptake and metabolism in isolated perfused lung: identification and comparison with prostaglandin F2α. Biochim. Biophys. Acta 712: 315–325, 1982.
 243. Rosenthale, M. E., A. Dervinis, and J. Kassarich. Bronchodilator activity of prostaglandins E1 and E2. J. Pharmacol. Exp. Ther. 178: 541–548, 1971.
 244. Roth, G. J., and P. W. Majerus. The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J. Clin. Invest. 56: 624–628, 1975.
 245. Roth, J. A., and J. C. Venter. Predominance of the B form of monoamine oxidase in cultured vascular intimal endothelial cells. Biochem. Pharmacol. 27: 2371–2372, 1978.
 246. Ryan, J. W., and U. S. Ryan. Pulmonary endothelial cells. Federation Proc. 36: 2683–2691, 1977.
 247. Sackeyfio, A. C. Anaphylatoxin‐induced release of a substance with prostaglandin‐like activity in isolated perfused guinea‐pig lungs (Abstract). Br. J. Pharmacol. 46: 544P–545P, 1972.
 248. Said, S. I. (editor). Prostaglandins and the lung. Bull. Eur. Physiopathol. Respir. 17: 487–736, 1981.
 249. Said, S. I., T. Yoshida, S. Kitamura, and C. Vreim. Pulmonary alveolar hypoxia: release of prostaglandins and other humoral mediators. Science 185: 1181–1183, 1974.
 250. Samuelsson, B., S. Hammarström, R. C. Murphy, and P. Borgeat. Leukotrienes and slow reacting substance of anaphylaxis (SRS‐A). Allergy 35: 375–381, 1980.
 251. Sanner, J. H. Substances that inhibit the actions of prostaglandins. Arch. Intern. Med. 133: 133–146, 1974.
 252. Saunders, C. R., E. R. Rittenhouse, B. M. Jaffe, and D. B. Doty. Prostaglandin E biosynthesis during cardiopulmonary bypass. J. Surg. Res. 24: 188–192, 1978.
 253. Simberg, N., H. Toivonen, J. Hartiala, and Y. S. Bakhle. The inactivation of prostaglandin E2 and 5‐hydroxytryptamine in isolated perfused fetal and neonatal rabbit lungs. Acta Physiol. Scand. 113: 291–295, 1982.
 254. Sinzinger, H., W. Feigh, and K. Silberbauer. Prostacyclin generation in atherosclerotic arteries. Lancet 2: 469, 1979.
 255. Smith, A. P., and M. F. Cuthbert. The antagonistic action of prostaglandin F2α and E2 aerosols on bronchial tone in man. Br. Med. J. 3: 212–213, 1972.
 256. Smith, A. P., M. F. Cuthbert, and L. S. Dunlop. Effects of inhaled prostaglandins E1, E2 and F2α on the airway resistance of healthy and asthmatic man. Clin. Sci. Mol. Med. 48: 421–430, 1975.
 257. Smith, A. P., and L. S. Dunlop. Prostaglandins and asthma (Letter). Lancet 1: 39, 1975.
 258. Smith, J. B., and A. L. Willis. Aspirin selectively inhibits prostaglandin production in human platelets. Nature London New Biol. 231: 235–237, 1971.
 259. Smith, M. J. H., A. W. Ford‐Hutchinson, and M. A. Bray. Leukotriene B: a potent mediator of inflammation. J. Pharm. Pharmacol. 32: 517–518, 1980.
 260. Sors, H., and P. Even. Biosynthesis and metabolism of prostaglandins and related compounds by the lung. In: Scientific Foundations of Respiratory Medicine, edited by J. G. Scadding, G. Cumming, and W. M. Thurlbeck. London: Heinemann, 1981, p. 297–315.
 261. Spannhake, E. W., A. L. Hyman, and P. J. Kadowitz. Dependence of the airway and pulmonary vascular effects of arachidonic acid upon route and rate of administration. J. Pharmacol. Exp. Ther. 212: 584–590, 1980.
 262. Spannhake, E. W., R. J. Lemen, M. J. Wegmann, A. L. Hyman, and P. J. Kadowitz. Analysis of airway effects of a PGH2 analog in the anesthetized dog. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 406–415, 1978.
 263. Spannhake, E. W., J. L. Levin, D. B. McNamara, A. L. Hyman, and P. Kadowitz. In vivo synthesis of airway‐active agents from arachidonic acid. Bull. Eur. Physiopathol. Respir. 17: 523–530, 1981.
 264. Splawinski, J., and R. J. Gryglewski. Release of prostacyclin by the lung. Bull. Eur. Physiopathol. Respir. 17: 553–570, 1981.
 265. Stalcup, S. A., L. M. Pang, J. S. Lipset, C. E. Odya, T. L. Goodfriend, and R. B. Mellins. Gestational changes in pulmonary converting enzyme activity in the fetal rabbit. Circ. Res. 43: 705–711, 1978.
 266. Steiner, M. Platelet protein synthesis studied in a cell‐free system. Experientia 26: 786–789, 1970.
 267. Sun, F. F., and S. B. Armour. Prostaglandin 15‐hydroxydehydrogenase and Δ13 reductase levels in the lungs of maternal, fetal and neonatal rabbits. Prostaglandins 7: 327–338, 1974.
 268. Sun, F. F., S. B. Armour, V. R. Bockstanz, and J. C. McGuire. Studies on 15‐hydroxyprostaglandin dehydrogenase from monkey lung. Adv. Prostaglandin Thromboxane Res. 1: 163–169, 1976.
 269. Sun, F. F., J. P. Chapman, and J. C. McGuire. Metabolism of prostaglandin endoperoxide in animal tissues. Prostaglandins 14: 1055–1074, 1977.
 270. Svensson, J. Structure and quantitative determination of the major urinary metabolite of thromboxane B2 in the guinea pig. Prostaglandins 17: 351–365, 1979.
 271. Svensson, J., M. Hamberg, and B. Samuelsson. Prostaglandin endoperoxides IX. Characterization of rabbit aorta contracting substance (RCS) from guinea pig lung and human platelets. Acta Physiol. Scand. 94: 222–228, 1975.
 272. Sweatman, W. O. J., and H. O. J. Collier. Effects of prostaglandins on human bronchial muscle. Nature London 217: 69, 1968.
 273. Szczeklik, A., and R. J. Gryglewski. Prostaglandins and aspirin‐sensitive asthma. Am. Rev. Respir. Dis. 118: 799–800, 1978.
 274. Szczeklik, A., and R. J. Gryglewski. Treatment of vascular disease with prostacyclin. In: Clinical Pharmacology of Prostacyclin, edited by P. J. Lewis and J. O'Grady. New York: Raven, 1981, p. 159–167.
 275. Szczeklik, A., R. J. Gryglewski, E. Nizankowska, R. Nizankowska, and J. Musial. Pulmonary and anti‐platelet effects of intravenous and inhaled prostacyclin in man. Prostaglandins 16: 654–660, 1978.
 276. Szczeklik, A., R. Nizankowski, S. Skawinski, J. Szczeklik, P. Gluszko, and R. J. Gryglewski. Successful therapy of advanced arteriosclerosis obliterans with prostacyclin. Lancet 1: 1111–1114, 1979.
 277. Tai, H. H. Biosynthesis and metabolism of pulmonary prostaglandins, thromboxanes and prostacyclin. Bull. Eur. Physiopathol. Respir. 17: 627–646, 1981.
 278. Tai, H. H., B. Yuan, and M. Sun. Metabolism of prostaglandins in spontaneously hypertensive rats: NAD+‐dependent 15‐hydroxyprostaglandin dehydrogenase activity is decreased in kidney and increased in lung. Life Sci. 24: 1275–1280, 1979.
 279. Toivonen, H., J. Hartiala, and Y. S. Bakhle. Effects of high oxygen tension on the metabolism of vasoactive hormones in isolated perfused rat lung. Acta Physiol. Scand. 111: 185–192, 1981.
 280. Vaage, J., L. Bjertnaes, and A. Hauge. The pulmonary vasoconstrictor response to hypoxia: effects of inhibitors of prostaglandin biosynthesis. Acta Physiol. Scand. 95: 95–101, 1975.
 281. Vader, C. R., M. M. Mathias, and C. L. Schatte. Pulmonary prostaglandin metabolism during normobaric hyperoxia. Prostaglandins Med. 6: 101–110, 1981.
 282. Vanderhoek, J. Y., and W. E. M. Lands. Acetylenic inhibitors of sheep vesicular gland oxygenase. Biochim. Biophys. Acta 296: 274–281, 1973.
 283. Van Dorp, D. A. Aspects of the biosynthesis of prostaglandins. Prog. Biochem. Pharmacol. 3: 171–182, 1967.
 284. Vane, J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin‐like drugs. Nature London New Biol. 231: 232–235, 1971.
 285. Vargaftig, B. B. Carrageenan and thrombin trigger prostaglandin synthetase‐independent aggregation of rabbit platelets: inhibition by phospholipase A2 inhibitors. J. Pharm. Pharmacol. 29: 222–228, 1977.
 286. Vargaftig, B. B., M. Chignard, J. M. Mercia‐Huerta, B. Arnoux, and J. Beneviste. Pharmacology of arachidonate metabolites and of platelet‐activating factor (PAF‐acether). In: Platelets in Biology and Pathology, edited by J. L. Gordon. Amsterdam: Elsevier/North‐Holland, 1981, vol. 2, p. 373–408.
 287. Vargaftig, B. B., and N. Dao‐Hai. Release of vasoactive substances from guinea‐pig lungs by slow reacting substance C and arachidonic acid. Pharmacology 6: 99–108, 1971.
 288. Von Euler, U. S. On the specific vasodilating and plain muscle stimulating substance from accessory genital glands in man and certain animals (prostaglandin and vesiglandin). J. Physiol. London 94: 187–226, 1938.
 289. Walker, J. L. The regulatory role of prostaglandins in the release of histamine and SRS‐A from passively sensitized human lung tissue. In: Advances in the Biosciences, edited by S. Bergström and S. Bernhard New York: Pergamon, 1973, vol. 9, p. 235–239.
 290. Walker, J. R., J. R. Boot, B. Cox, and W. Dawson. Inhibition of the release of slow reacting substance of anaphylaxis by inhibitors of lipoxygenase activity. J. Pharm. Pharmacol. 32: 866–867, 1980.
 291. Walker, J. R., and W. Dawson. Inhibition of rabbit PMN lipoxygenase activity by benoxaprofen. J. Pharm. Pharmacol. 31: 778–780, 1979.
 292. Wasserman, M. A. Bronchopulmonary pharmacology of some prostaglandin endoperoxide analogs in the dog. Eur. J. Pharmacol. 36: 103–114, 1976.
 293. Wasserman, M. A., D. W. Ducharme, M. G. Wendeling, R. L. Griffin, and G. L. Graaf. Bronchodilator effects of prostacyclin (PGI2) in dogs and guinea pigs. Eur. J. Pharmacol. 66: 53–58, 1980.
 294. Wedmore, C. V., and T. J. Williams. Control of vascular permeability by polymorphonuclear leukocytes in inflammation. Nature London 284: 646–650, 1981.
 295. Weir, E. K., I. F. McMurtry, A. Tucker, J. T. Reeves, and R. F. Grover. Prostaglandin synthetase inhibitors do not decrease hypoxic pulmonary vasoconstriction. J. Appl. Physiol. 41: 714–718, 1976.
 296. Wicks, T. C., J. C. Rose, M. Johnson, P. W. Ramwell, and P. A. Kot. Vascular responses to arachidonic acid in the perfused canine lung. Circ. Res. 38: 167–171, 1976.
 297. Williams, K. I., K. E. H. El‐Tahir, and E. Marcinkiewicz. Dual actions of prostacyclin (PGI2) on the rat pregnant uterus. Prostaglandins 17: 667–672, 1979.
 298. Williams, T. J., and P. J. Jose. Mediation of increased vascular permeability after complement activation. J. Exp. Med. 153: 136–153, 1981.
 299. Williams, T. J., and M. J. Peck. Role of prostaglandin‐mediated vasodilation in inflammation. Nature London 270: 530–532, 1977.
 300. Willis, A. L. Parallel assay of prostaglandin‐like activities in rat inflammatory exudate by means of cascade superfusion. J. Pharm. Pharmacol. 21: 126–128, 1969.
 301. Woods, H. F., G. Ash, M. J. Weston, S. Bunting, S. Moncada, and J. R. Vane. Prostacyclin can replace heparin in haemodialysis in dogs. Lancet 2: 1075–1077, 1978.
 302. Youdim, M. B. H., Y. S. Bakhle, and R. R. Ben‐Harari. Inactivation of monoamines by the lung. In: Metabolic Activities of the Lung, edited by R. Porter and J. Whelan Amsterdam: Excerpta Med., 1980, p. 105–128. (Ciba Found. Symp. 78.)

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Lung Metabolism of Eicosanoids: Prostaglandins, Prostacyclin, Thromboxane, and Leukotrienes
 

How to Cite

Y. S. Bakhle, Sergio H. Ferreira. Lung Metabolism of Eicosanoids: Prostaglandins, Prostacyclin, Thromboxane, and Leukotrienes. Compr Physiol 2011, Supplement 10: Handbook of Physiology, The Respiratory System, Circulation and Nonrespiratory Functions: 365-386. First published in print 1985. doi: 10.1002/cphy.cp030111