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Altered Permeability of Cell Membranes

W. B. Kinter, J. B. Pritchard

10.1002/cphy.cp090136

Source: Supplement 26: Handbook of Physiology, Reactions to Environmental Agents

Originally published: 1977

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Membrane Theory of Toxicity
2 Heavy Metals — Mercury and its Compounds
2.1 Passive Ion and Water Permeability of Cells
2.2 Carrier‐Mediated Ion Transport
2.3 Inhibition of Other Transport Systems
2.4 Environmental Role
3 Organochlorines — DDT and its Metabolites
3.1 Passive Na+ and K+ Permeability of Axolemma
3.2 Active Na+ Transport in Epithelia and Cells
3.3 Inhibition of Other Active Transport Systems
4 Conclusions and Speculations
Figure 1. Figure 1.

Schematic and simplified diagram of generalized cell membrane showing permeability pathways. In mosaic of lipids and proteins composing the membrane, hydrophobic portions of these molecules (stippled) are in the interior; hydrophilic portions (unstippled) constitute the interface between membrane and aqueous media and contain the functional protein groups regulating both passive and carrier‐mediated permeability pathways. Top: ion‐specific aqueous channels, gates, or pores through hydrophilic regions of the membrane used for passive (downhill) movement of electrolytes (and some small water‐soluble nonelectrolytes as well) across the membrane. Associated sulfhydryl (SH) and amino () groups affect the regulation of permeability. Hydrophobic regions of the membrane are used for movement of lipid‐soluble substances. Bottom: representative carrier‐mediated processes. Thick arrows, active transport, i.e., movement against an electrochemical gradient that requires coupling to metabolic energy. This coupling may be either to ATP hydrolysis directly (Na+ pump) or to an ion gradient maintained by a separate pump (Na‐coupled cycloleucine transport). Thin arrows, movement down the electrochemical gradient of the substrate. Black areas at membrane surface, binding sites on carrier for substrate or coupled ion. Sodium pump is shown as electrogenic, yet in many instances active sodium transport is accompanied by simultaneous movement of potassium in the opposite direction. Actual directions of transport into or out of the cell have been ignored.

Adapted from Rothstein et al. 150
Figure 2. Figure 2.

Inhibition of Na‐dependent (unstippled) cycloleucine accumulation in intestinal tissue of killifish (Fundulus heteroclitus) exposed in vivo to DDT. All fish were adapted to seawater; just prior to removal of tissue for in vitro study, experimental group was exposed for 4 h to 0.075 ppm p,p′‐DDT suspended in seawater by sonication. Continued exposure to this level of DDT for 48 h produced 50% mortality in seawater‐adapted killifish 94. In study of intestinal transport, cycloleucine is commonly employed to evaluate the neutral amino acid system or systems, since it is nonmetabolized and transported rapidly enough across the brush border into epithelial cells so that these cells can be assumed to be the primary site of tissue uptake during brief incubation in vitro. Present results indicate that, in addition to being DDT‐sensitive, the Na‐dependent component of cycloleucine uptake represents active (uphill) transport against a concentration gradient — i.e., causes the tissue‐to‐medium concentration ratio to exceed unity. Other results (not shown) indicate that this uptake component was fully inhibitable by several naturally occurring neutral amino acids, e.g., leucine, alanine, proline and glycine, and was partially inhibitable by taurine and 3‐amino proprionic acid (β‐alanine). In contrast, the minor Na‐independent component (stippled) was insensitive to neutral amino acids as well as to DDT and probably represents passive diffusion into cells.
Figure 3. Figure 3.

Inhibition of ion‐activated ATPase fractions in duck shell‐gland homogenate by 1,1‐dichloro‐2,2‐bis(p‐chlorophenyl)ethylene (DDE) added in vitro to assay media. Each point represents the mean of 3–10 conventional ATPase assays on tissue from normal, laying domestic ducks (Anas platyrynchos). Mucosal scrapings from freshly killed birds were homogenized, freeze‐dried, and reconstituted in several media, each having the proper ion composition for maximum activation of a particular ATPase. For the anion‐activated enzyme, sulfite was employed, for it yielded more ATPase activity than bicarbonate. DDE concentration was based on quantity added to assay media; 0.5% N,N‐dimethylformamide provided solubilization in the media. Control rates of ATP hydrolysis were measured in the presence of the solvent alone.


Figure 1.

Schematic and simplified diagram of generalized cell membrane showing permeability pathways. In mosaic of lipids and proteins composing the membrane, hydrophobic portions of these molecules (stippled) are in the interior; hydrophilic portions (unstippled) constitute the interface between membrane and aqueous media and contain the functional protein groups regulating both passive and carrier‐mediated permeability pathways. Top: ion‐specific aqueous channels, gates, or pores through hydrophilic regions of the membrane used for passive (downhill) movement of electrolytes (and some small water‐soluble nonelectrolytes as well) across the membrane. Associated sulfhydryl (SH) and amino () groups affect the regulation of permeability. Hydrophobic regions of the membrane are used for movement of lipid‐soluble substances. Bottom: representative carrier‐mediated processes. Thick arrows, active transport, i.e., movement against an electrochemical gradient that requires coupling to metabolic energy. This coupling may be either to ATP hydrolysis directly (Na+ pump) or to an ion gradient maintained by a separate pump (Na‐coupled cycloleucine transport). Thin arrows, movement down the electrochemical gradient of the substrate. Black areas at membrane surface, binding sites on carrier for substrate or coupled ion. Sodium pump is shown as electrogenic, yet in many instances active sodium transport is accompanied by simultaneous movement of potassium in the opposite direction. Actual directions of transport into or out of the cell have been ignored.

Adapted from Rothstein et al. 150


Figure 2.

Inhibition of Na‐dependent (unstippled) cycloleucine accumulation in intestinal tissue of killifish (Fundulus heteroclitus) exposed in vivo to DDT. All fish were adapted to seawater; just prior to removal of tissue for in vitro study, experimental group was exposed for 4 h to 0.075 ppm p,p′‐DDT suspended in seawater by sonication. Continued exposure to this level of DDT for 48 h produced 50% mortality in seawater‐adapted killifish 94. In study of intestinal transport, cycloleucine is commonly employed to evaluate the neutral amino acid system or systems, since it is nonmetabolized and transported rapidly enough across the brush border into epithelial cells so that these cells can be assumed to be the primary site of tissue uptake during brief incubation in vitro. Present results indicate that, in addition to being DDT‐sensitive, the Na‐dependent component of cycloleucine uptake represents active (uphill) transport against a concentration gradient — i.e., causes the tissue‐to‐medium concentration ratio to exceed unity. Other results (not shown) indicate that this uptake component was fully inhibitable by several naturally occurring neutral amino acids, e.g., leucine, alanine, proline and glycine, and was partially inhibitable by taurine and 3‐amino proprionic acid (β‐alanine). In contrast, the minor Na‐independent component (stippled) was insensitive to neutral amino acids as well as to DDT and probably represents passive diffusion into cells.



Figure 3.

Inhibition of ion‐activated ATPase fractions in duck shell‐gland homogenate by 1,1‐dichloro‐2,2‐bis(p‐chlorophenyl)ethylene (DDE) added in vitro to assay media. Each point represents the mean of 3–10 conventional ATPase assays on tissue from normal, laying domestic ducks (Anas platyrynchos). Mucosal scrapings from freshly killed birds were homogenized, freeze‐dried, and reconstituted in several media, each having the proper ion composition for maximum activation of a particular ATPase. For the anion‐activated enzyme, sulfite was employed, for it yielded more ATPase activity than bicarbonate. DDE concentration was based on quantity added to assay media; 0.5% N,N‐dimethylformamide provided solubilization in the media. Control rates of ATP hydrolysis were measured in the presence of the solvent alone.

References
 1. Akera, T., T. M. Brody, and N. Leeling. Insecticide inhibition of Na‐K‐ATPase activity. Biochem. Pharmacol. 20: 471–473, 1971.
 2. Angle, C. R., and M. S. McIntire. Red cell lead, whole blood lead, and red cell enzymes. Environ. Health Perspect. 7: 133–137, 1974.
 3. Avery, J. (editor)., Membrane Structure and Mechanisms of Biological Energy Transduction. London: Plenum Press, 1973.
 4. Baker, P. F., The sodium pump in animal tissues and its role in the control of cellular metabolism and function. In: Metabolic Transport; Metabolic Pathways (3rd ed.), edited by D. M. Greenberg. New York: Academic Press, 1972, vol. 6, p. 243‐268.
 5. Bakri, M., and Govindjee. Effects of lead on chloroplast reactions. Environ. Letters 6: 175–191, 1971.
 6. Ball, E. G. Hemolytic action of silver occuring as an impurity in chemically pure sodium chloride. Biol. Bull. 64: 277–288, 1933.
 7. Barbeau, A., and J. Donaldson. Zinc, taurine, and epilepsy. Arch. Neurol. 30: 52–58, 1974.
 8. Barnola, F. V., G. Camejo, and R. Villegas. Ionic channels and nerve membrane lipoproteins: DDT‐nerve membrane interaction. Intern. J. Neurosci. 1: 309–316, 1971.
 9. Batterton, J. C., G. M. Boush, and F. Matsumura. Growth response of blue‐green algae to aldrin, dieldrin, endrin and their metabolites. Bull. Environ. Contamination Toxicol. 6: 589–594, 1971.
 10. Batterton, J. C., G. M. Boush, and F. Matsumura. DDT: Inhibition of sodium chloride tolerance by the blue‐green alga Anacystis nidulans. Science 176: 1141–1143, 1972.
 11. Begenisich, T., and C. Lynch. Effects of internal divalent cations on voltage‐clamped squid axons. J. Gen. Physiol. 63: 675–689, 1974.
 12. Benesch, R. E., and R. Benesch. Relation between erythrocyte integrity and sulfhydryl groups. Arch. Biochem. 48: 38–42, 1954.
 13. van den Bercken, J. The effect of DDT and dieldrin on myelinated nerve fibres. European J. Pharmacol. 20: 205–214, 1972.
 14. Berglund, F., and M. Berlin. Risk of methylmercury cumulation in man and mammals and the relation between body burden of methylmercury and toxic effects. In: Chemical Fallout, edited by M. W. Miller and G. G. Berg. Springfield, Ill.: Thomas, 1969, p. 258‐273.
 15. Bonting, S. L., Sodium‐potassium activated adenosinetriphosphatase and cation transport. In: Membranes and Ion Transport, edited by E. E. Bittar. London: Wiley, 1970, vol. 1, p. 257‐363.
 16. Bostrom, S. L., and R. G. Johansson. Effects of pentachlorophenol on enzymes involved in energy metabolism in the liver of the eel. Comp. Biochem. Physiol. Part B 41: 359–369, 1972.
 17. Bowman, F. J., and E. J. Landon. Organic mercurials and net movements of potassium in rat kidney slices. Am. J. Physiol. 213: 1209–1217, 1967.
 18. Brierley, G. P., V. A. Knight, and C. T. Settlemire. Ion transport by heart mitochondria. XII. Activation of monovalent cation uptake by sulfhydryl group reagents. J. Biol. Chem. 243: 5035–5043, 1968.
 19. Brunnert, H., and F. Matsumura. Binding of 1,1,1‐trichloro‐2,2‐di‐p‐chlorophenylethane (DDT) with subcellular fractions of rat brain. Biochem. J. 114: 135–139, 1969.
 20. Burg, M., and N. Green. Effect of mersalyl on the thick ascending limb of Henle's loop. Kidney Intern. 4: 245–251, 1973.
 21. Burns, M. J., and R. G. Faust. Preferential binding of amino acids to isolated mucosal brush borders from hamster jejunum. Biochim. Biophys. Acta 183: 642–645, 1969.
 22. Cafruny, E. J. The site and mechanism of action of mercurial diuretics. Pharmacol. Rev. 20: 89–116, 1968.
 23. Campbell, R. D., T. P. Leadem, and D. W. Johnson. The in vivo effect of p,p' DDT on Na+‐K+‐activated ATPase activity in rainbow trout (Salmo gairdneri). Bull. Environ. Contamination Toxicol. 11: 425–428, 1974.
 24. Carter, E. A., and K. J. Isselbacher. Effect of ethanol on intestinal adenosine triphosphate (ATP) content. Proc. Soc. Exptl. Biol. Med. 142: 1171–1173, 1973.
 25. Carter, J. R., Jr.. Role of sulfhydryl groups in erythrocyte membrane structure. Biochemistry 12: 171–176, 1973.
 26. Chan, P. C., and M. S. Rosenblum. Effect of sulfhydryl group modification of erythrocyte membrane adenosine triphosphatase. Proc. Soc. Exptl. Biol. Med. 130: 143–145, 1969.
 27. Cheng, E. Y., and L. K. Cutkomp. Ageing in the honeybee, Apis mellifera, as related to brain ATPases and their DDT sensitivity. J. Insect Physiol. 18: 2285–2291, 1972.
 28. Clarkson, T. W. The pharmacology of mercury compounds. Ann. Rev. Pharmacol. 12: 375–406, 1972.
 29. Cooke, A. S. Shell thinning in avian eggs by environmental pollutants. Environ. Pollut. 4: 85–152, 1973.
 30. Cutkomp, L. K., H. H. Yap, E. Y. Cheng, and R. B. Koch. ATPase activity in fish tissue homogenates and inhibitory effects of DDT and related compounds. Chem.‐Biol. Interact. 3: 439–447, 1971.
 31. Cutkomp, L. K., H. H. Yap, D. Desaiah, and R. B. Koch. The sensitivity of fish ATPases to polychlorinated biphenyls. Environ. Health Perspectives 1: 165–168, 1972.
 32. Cutkomp, L. K., H. H. Yap, E. V. Vea, and R. B. Koch. Inhibition of oligomycin‐sensitive (mitochondrial) Mg2+ ATPase by DDT and selected analogs in fish and insect tissue. Life Sci. Part 2 10: 1201–1209, 1971.
 33. Davis, P. W., J. M. Friedhoff, and G. A. Wedemeyer. Organochlorine insecticide, herbicide and polychlorinted biphenyl (PCB) inhibition of NaK‐ATPase in rainbow trout. Bull. Environ. Contamination Toxicol. 8: 69–72, 1972.
 34. Davis, P. W., and G. A. Wedemeyer. Na+, K+‐activated‐ATPase inhibition in rainbow trout: A site for organochlorine pesticide toxicity? Comp. Biochem. Physiol. Part B 40: 823–827, 1971.
 35. Delaney, M. E., W. J. Owen, and L. J. Rogers. Inhibition of photosynthetic electron transport by 1,1,1‐trichloro‐2,2‐bis‐(p‐chlorophenyl)ethane (DDT) at a site before photosystem 2. Biochem. J. 124: 24p‐25p, 1971.
 36. Demopoulos, H. B. The basis of free radical pathology. Federation Proc. 32: 1859–1861, 1973.
 37. Demopoulos, H. B. Control of free radicals in biologic systems. Federation Proc. 32: 1903–1908, 1973.
 38. Desaiah, D., L. K. Cutkomp, R. B. Koch, and H. H. Yap. Tetradifon (Tedion): A specific inhibitor of Mg2+ dependent mitochondrial adenosine triphosphatase activity. Life Sci. Part 2 11: 389–395, 1972.
 39. Desaiah, D., L. K. Cutkomp, H. H. Yap, and R. B. Koch. Inhibition of oligomycin‐sensitive and ‐insensitive magnesium adenosine triphosphatase activity in fish by polychlorinated biphenyls. Biochem. Pharmacol. 21: 857–865, 1972.
 40. DiLuzio, N. R. Antioxidants, lipid peroxidation and chemical‐induced liver injury. Federation Proc. 32: 1875–1881, 1973.
 41. Dupont, Y., and W. Hasselbach. Structural changes in sarcoplasmic reticulum membrane induced by SH reagents. Nature 246: 41–44, 1973.
 42. Edman, K. A. P., D. W. Grieve, and E. Nilsson. Studies of the excitation‐contraction mechanism in the skeletal muscle and the myocardium. Pfluegers Arch. Ges. Physiol. 290: 320–334, 1966.
 43. Eisler, R., and P. H. Edmunds. Effects of endrin on blood and tissue chemistry of a marine fish. Trans. Am. Fisheries Soc. 95: 153–159, 1966.
 44. Ewing, R. D., G. L. Peterson, and F. P. Conte. Larval salt gland of Artemia salina nauplii: Localization and characterization of the sodium + potassium‐activated adenosine triphosphatase. J. Comp. Physiol. 88: 217–234, 1974.
 45. Fanelli, G. M., Jr., D. L. Bohn, and S. S. Reilly. Effects of mercurial diuretics on the renal tubular transport of p‐amino‐hippurate and diodrast in the chimpanzee. J. Pharmacol. Exptl. Therap. 180: 759–766, 1972.
 46. Forster, R. P. Renal transport mechanisms. Federation Proc. 26: 1008–1019, 1967.
 47. Foulkes, E. C. Effects of heavy metals on renal aspartate transport and the nature of solute movement in kidney cortex slices. Biochim. Biophys. Acta 241: 815–822, 1971.
 48. Foulkes, E. C. Glomerular filtration and renal plasma flow in uranium poisoned rabbits. Toxicol. Appl. Pharmacol. 20: 380–385, 1971.
 49. Foulkes, E. C., Site of the functional lesion responsible for amino‐aciduria after administration of organomercurials and other metal compounds. In: Mercury, Mercurials and Mercaptans, edited by M. W. Miller and T. W. Clarkson. Springfield, Ill.: Thomas, 1973, p. 99‐110.
 50. Fox, C. F., and E. P. Kennedy. Specific labeling and partial purification of the M protein, a component of the betagalactoside transport system of Escherichia coli. Proc. Natl. Acad. Sci. US 54: 891–899, 1965.
 51. Friend, M., M. A. Haegele, and R. Wilson. DDE: Interference with extra‐renal salt excretion in the mallard. Bull. Environ. Contamination Toxicol. 9: 49–53, 1973.
 52. Frizzell, R. A., and S. G. Schultz. Effects of monovalent cations on the sodium‐alanine interaction of rabbit ileum: Implication of anionic groups in sodium binding. J. Gen. Physiol. 56: 462–490, 1970.
 53. Garrahan, P. J., and A. F. Rega. Cation loading of red blood cells. J. Physiol. London 193: 459–466, 1967.
 54. Gieske, T. H., and E. C. Foulkes. Cadmium inhibition of amino acid transport in rabbit kidney. Federation Proc. 32: 381, 1973.
 55. Glick, N. B., Inhibition of transport reactions. A. Inhibitors of ATPase: NaK‐ATPase and related enzymic activities. In: Metabolic Inhibitors, edited by R. M. Hochster, M. Kates and J. H. Quastel. New York: Academic Press, 1973, vol. III, p. 1‐45.
 56. Godin, D. V., and S. L. Schrier. Modification of the erythrocyte membrane by sulfhydryl group reagents. J. Membrane Biol. 7: 285–312, 1972.
 57. Goldberg, M., The renal physiology of diuretics. In: Handbook of Physiology. Renal Physiology, edited by J. Orloff and R. W. Berliner. Washington, D.C.: Am. Physiol. Soc., 1973, sect. 8, chapt. 28, p. 1003‐1031.
 58. Goyer, R. A., and B. C. Rhyne. Pathological effects of lead. Intern. Rev. Exptl. Pathol. 12: 1–77, 1973.
 59. Grant, B. F., and P. M. Mehrle. Chronic endrin poisoning in goldfish, Carassius auratus. J. Fisheries Res. Board Can. 27: 2225–2232, 1970.
 60. Grant, B. F., and P. M. Mehrle. Endrin toxicity in rainbow trout (Salmo gairdneri). J. Fisheries Res. Board Can. 30: 31‐40, 1973.
 61. Green, F. A. Sulfhydryl reagents and lecithin binding to butanol‐extracted membranes. Chem. Phys. Lipids 10: 309–317, 1973.
 62. Gruppuso, P. A., and L. B. Kinter. DDT inhibition of active chlorophenol red transport in goldfish (Carassius auratus) renal tubules. Bull. Environ. Contamination Toxicol. 10: 181–186, 1973.
 63. Guerrero, S., and W. K. Riker. Effects of divalent cations on frog sympathetic ganglion. Federation Proc. 31: 509, 1972.
 64. Haque, R., I. J. Tinsley, and D. Schmedding. Lipid binding and mode of action of compounds of the dichlorodiphenyltrichloroethane type: A proton magnetic resonance study. Mol. Pharmacol. 9: 17–22, 1973.
 65. Hasan, J., and S. Hernberg. Deficient red cell membrane (Na+ + K+)‐ATPase in lead poisoning. Arch. Environ. Health 14: 313–318, 1967.
 66. Hays, R. M. Independent pathways for water and solute movement across the cell membrane. J. Membrane Biol. 10: 367–371, 1972.
 67. Heinz, E. (editor)., Na‐Linked Transport of Organic Solutes. Berlin: Springer‐Verlag, 1972. (Symposium.).
 68. Heinz, E., Transport of amino acids by animal cells. In: Metabolic Transport; Metabolic Pathways (3rd ed.), edited by D. M. Greenberg. New York: Academic Press, 1972, vol. 6, p. 455‐501.
 69. Hille, B. Pharmacological modifications of the sodium channels of frog nerve. J. Gen. Physiol. 51: 199–219, 1968.
 70. Hillman, R. E., and L. E. Rosenberg. Amino acid transport by isolated mammalian renal tubules. III. Binding of 1‐proline by proximal tubule membranes. Biochim. Biophys. Acta 211: 318–326, 1970.
 71. Hilton, B. D., T. A. Bratkowski, M. Yamada, T. Narahashi, and R. D. O'Brien. The effects of DDT analogs upon potassium conductance in synthetic membranes. Pesticide Biochem. Physiol. 3: 14–19, 1973.
 72. Hilton, B. D., and R. D. O'Brien. Antagonism by DDT of the effect of valinomycin on a synthetic membrane. Science 168: 841–843, 1970.
 73. Hilton, B. D., and R. D. O'Brien. The effects of DDT and its analogs upon lecithin and other monolayers. Pesticide Biochem. Physiol. 3: 206–213, 1973.
 74. Hirsch, G. H. Inhibition of renal organic ion transport by methylmercury. Environ. Physiol. 1: 51–54, 1971.
 75. Hirsch, G. H. Differential effects of nephrotoxic agents on renal organic ion transport and metabolism. J. Pharmacol. Exptl. Therap. 186: 593–599, 1973.
 76. Hoffman, P. G., and D. C. Tosteson. Active sodium and potassium transport in high potassium and low potassium sheep red cells. J. Gen. Physiol. 58: 438–466, 1971.
 77. Hokin, L. E., and J. L. Dahl. The sodium‐potassium adenosinetriphosphatase. In: Metabolic Transport; Metabolic Pathways (3rd ed.), edited by D. M. Greenberg. New York: Academic Press, 1972, vol. 6, p. 269‐315.
 78. Holan, G. New halocyclopropane insecticides and the mode of action of DDT. Nature 221: 1025–1029, 1969.
 79. Holan, G. Rational design of insecticides. Bull. World Health Organ. 44: 355–362, 1971.
 80. Holden, A. V., Effects of pesticides on fish. In: Environmental Pollution by Pesticides, edited by C. A. Edwards. London: Plenum Press, 1973, p. 213‐253. (Environ. Sci. Res. Ser., vol. 3.).
 81. Hook, J. B., and G. H. Hirsch. Effects of organic mercurial compounds on renal organic ion transport. In: Mercury, Mercurials and Mercaptans, edited by M. W. Miller and T. W. Clarkson. Springfield, Ill.: Thomas, 1973, p. 124‐138.
 82. Huneeus‐Cox, F., H. L. Fernandez, and B. H. Smith. Effects of redox and sulfhydryl reagents on the bioelectric properties of the giant axon of the squid. Biophys. J. 6: 675–689, 1966.
 83. Hunter, F. R., J. George, and B. Ospina. Possible carriers in erythrocytes. J. Cellular Comp. Physiol. 65: 299–312, 1965.
 84. Jackson, D. A., and D. R. Gardner. The effects of some organochlorine pesticide analogs on salmonid brain ATPases. Pesticide Biochem. Physiol. 2: 377–382, 1973.
 85. Jacob, H. S., and J. H. Jandl. Effects of sulfhydryl inhibition on red blood cells. I. Mechanism of hemolysis. J. Clin. Invest. 41: 779–792, 1962.
 86. Janicki, R. H., and W. B. Kinter. DDT: Disrupted osmoregulatory events in the intestine of the eel Anguilla rostrate adapted to seawater. Science 173: 1146–1148, 1971.
 87. Janicki, R. H., and W. B. Kinter. DDT: Effect on ATPase and water absorption in fish. Federation Proc. 30: 673, 1971.
 88. Janicki, R. H., and W. B. Kinter. DDT, DDE and DDD: Effects on ATPase activity in the rectal gland of the dogfish shark (Squalus acanthias). Bull. Mt. Desert Isl. Biol. Lab. 11: 49‐51, 1971.
 89. Janicki, R. H., and W. B. Kinter. DDT inhibits Na+, K+, Mg2+‐ATPase in the intestinal mucosae and gills of marine teleosts. Nature 233: 148–149, 1971.
 90. Johnson, D. W. Pesticides and fishes—A review of selected literature. Trans. Am. Fisheries Soc. 97: 398–424, 1968.
 91. Kagan, Y. S., S. I. Fudel‐Ossipova, B. J. Khaikina, U. A. Kuzmin‐Skaya, and S. D. Kouton. On the problem of the harmful effect of DDT and its mechanism of action. Residue Rev. 27: 43–79, 1969.
 92. Kamemoto, F. I., and R. E. Tullis. Hydromineral regulation in decapod Crustacea. Gen. Comp. Endocrinol. Suppl. 3: 299–307, 1972.
 93. Kerstetter, T. H., and L. B. Kirschner. HCO3‐‐dependent ATPase activity in the gills of rainbow trout (Salmo gairdneri). Comp. Biochem. Physiol. Part B 48: 581‐589, 1974.
 94. Kinter, W. B., L. S. Merkens, R. H. Janicki, and A. M. Guarino. Studies on the mechanism of toxicity of DDT and polychlorinated biphenyls (PCB's): Disruption of osmoregulation in marine fish. Environ. Health Perspectives 1: 169–173, 1972.
 95. Kleinzeller, A., and J. H. Cort. The mechanism of action of mercurial preparations on transport processes and the role of thiol groups in the cell membrane of renal tubular cells. Biochem. J. 67: 15–24, 1957.
 96. Knauf, P. A., and A. Rothstein. Chemical modification of membranes. I. Effects of sulfhydryl and amino reactive reagents on anion and cation permeability of the human red blood cell. J. Gen. Physiol. 58: 190–210, 1971.
 97. Knauf, P. A., and A. Rothstein. Chemical modication of membranes. II. Permeation paths for sulfhydryl agents. J. Gen. Physiol. 58: 211–223, 1971.
 98. Koch, R. B. Chlorinated hydrocarbon insecticides: Inhibition of rabbit brain ATPase activities. J. Neurochem. 16: 269–271, 1969.
 99. Koch, R. B. Inhibition of animal tissue ATPase activities by chlorinated hydrocarbon pesticides. Chem.‐Biol. Interact. 1: 199–209, 1969.
 100. Koch, R. B., L. K. Cutkomp, and F. M. Do. Chlorinated hydrocarbon insecticide inhibition of cockroach and honeybee ATPases. Life Sci. Part 2 8: 289–297, 1969.
 101. Koch, R. B., L. K. Cutkomp, and H. H. Yap. Inhibition of oligomycin sensitive and insensitive fish adenosine triphosphatase activity by chlorinated hydrocarbon insecticides. Biochem. Pharmacol. 20: 3243–3245, 1971.
 102. Koch, R. B., D. Desaiah, H. H. Yap, and L. K. Cutkomp. Polychlorinated biphenyls: Effect of long‐term exposure on ATPase activity in fish, Pimephales promelas. Bull. Environ. Contamination Toxicol. 7: 87–92, 1972.
 103. Leadem, T. P., R. D. Campbell, and D. W. Johnson. Osmoregulatory responses to DDT and varying salinities in Salmo gairdneri—I. Gill Na‐K‐ATPase. Comp. Biochem. Physiol. Part A 49: 197‐205, 1974.
 104. Lefevre, P. G., Transport of carbohydrates by animal cells. In: Metabolic Transport; Metabolic Pathways (3rd ed.), edited by D. M. Greenberg. New York: Academic Press, 1972, vol. 6, p. 385‐454.
 105. Lefevre, P. G., K. I. Habich, H. S. Hess, and M. R. Hudson. Phospholipid‐sugar complexes in relation to cell membrane monosaccharide transport. Science 143: 955–957, 1964.
 106. Lehninger, A. L. Biochemistry: The Molecular Basis of Cell Structure and Function. New York: Worth, 1970, p. 365‐416, 455‐480.
 107. Macey, R. I., and R. E. L. Farmer. Inhibition of water and solute permeability in human red cells. Biochim. Biophys. Acta 211: 104–106, 1970.
 108. Macey, R. I., D. M. Karan, and R. E. L. Farmer. Properties of water channels in human red cells. Biomembranes 3: 331–340, 1972.
 109. Manalis, R. S., and G. P. Cooper. Presynaptic and postsynaptic effects of lead at the frog neuromuscular junction. Nature 243: 354–355, 1973.
 110. Martin, K. Some properties of an SH group essential for choline transport in human erythrocytes. J. Physiol. London 213: 647–664, 1971.
 111. Matsumura, F. DDT action and adenosine triphosphaterelated systems. Science 169: 1343, 1970.
 112. Matsumura, F., and T. Narahashi. ATPase inhibition and electrophysiological change caused by DDT and related neuroactive agents in lobster nerve. Biochem. Pharmacol. 20: 825–837, 1971.
 113. Matsumura, F., and K. C. Patil. Adenosine triphosphatase sensitive to DDT in synapses of rat brain. Science 166: 121–122, 1969.
 114. Menzel, D. W., J. Anderson, and A. Randtke. Marine phytoplankton vary in their response to chlorinated hydrocarbons. Science 167: 1724–1726, 1970.
 115. Miller, D. S., D. B. Peakall, W. B. Kinter, and R. W. Risebrough. Minimal DDE effects on plasma osmoregulation and nasal gland Na‐K ATPase in ducks. Federation Proc. 33: 220, 1974.
 116. Miller, D. S., A. Seymour, D. Shoemaker, G. Maeda, D. B. Peakall, R. W. Risebrough, and W. B. Kinter. Minimal DDE‐disruption of osmoregulation in mallard type ducks Anas platyrhynchos. Bull. Mt. Desert Isl. Biol. Lab. 13: 77–79, 1973.
 117. Minemura, T., and O. B. Crofford. Insulin‐receptor interaction in isolated fat cells. I. The insulin‐like properties of p‐chloromercuribenze sulfonic acid. J. Biol. Chem. 244: 5181–5188, 1969.
 118. Molina, G., A. Farah, and R. Kruse. Effect of vasopressin and dehydration on protein‐bound sulfhydryl and disulfide groups in renal cells. Am. J. Physiol. 204: 541‐547, 1963.
 119. Mudge, G. H., W. O. Berndt, and H. Valtin. Tubular transport of urea, glucose, phosphate, uric acid, sulfate, and thiosulfate. In: Handbook of Physiology Renal Physiology, edited by J. Orloff, and R. W. Berliner. Washington, D.C.: Am. Physiol. Soc., 1973, sect. 8, chapt. 19, p. 587‐652.
 120. Naccache, P., and R. I. Sha'afi. Effect of PCMBS on water transfer across biological membranes. J. Cellular Physiol. 83: 449–456, 1974.
 121. Narahashi, T., Effects of insecticides on excitable tissues. In: Advances in Insect Physiology, edited by J. W. L. Beament, J. E. Treherne, and V. B. Wigglesworth. London: Academic Press, 1971, vol. 8, p. 1‐93.
 122. Narahashi, T., and H. G. Haas. Interaction of DDT with the components of lobster nerve membrane conductance. J. Gen. Physiol. 51: 177–198, 1968.
 123. Nechay, B. R., Action of mercury on renal sodium transport and adenosine triphosphatase activity. In: Mercury, Mercurials and Mercaptans, edited by M. W. Miller and T. W. Clarkson. Springfield, Ill.: Thomas, 1973, p. 111‐123.
 124. Nechay, B. R., R. F. Palmer, D.A. Chinoy, and V. A. Posey. The problem of Na+ and K+ adenosine triphosphatase as the receptor for diuretic action of mercurials and ethacrynic acid. J. Pharmacol. Exptl. Therap. 157: 599–616, 1967.
 125. Nomiyama, K., and E. C. Foulkes. Some effects of uranyl acetate on proximal tubular function in rabbit kidney. Toxicol. Appl. Pharmacol. 13: 89–98, 1968.
 126. O'Brien, R. D. Insecticides: Action and Metabolism. New York: Acadamic Press, 1967.
 127. Owen, W. J., and L. J. Rogers. Inhibition of photosynthetic electron transport by 1,1,1‐trichloro‐2,2‐bis(p‐chlorophenyl)ethane (DDT) at a site in the intermediate electron‐transport chain. Biochem. J. 125: 43p‐44p, 1971.
 128. Pardini, R. S. Polychlorinated biphenyls (PCB): Effect on mitochondrial enzyme systems. Bull. Environ. Contamination Toxicol. 6: 539–545, 1971.
 129. Pardini, R. S., J. C. Heidker, and B. Payne. The effect of some cyclodiene pesticides, benzenehexachloride and toxaphene on mitochondrial electron transport. Bull. Environ. Contamination Toxicol. 6: 436–444, 1971.
 130. Passow, H., A. Rothstein, and T. W. Clarkson. The general pharmacology of the heavy metals. Pharmacol. Rev. 13: 185–224, 1961.
 131. Payne, N. B., G. R. Herzberg, and J. L. Howland. Influence of some insecticides and the ATPase of mouse liver mitochondria. Bull. Environ. Contamination Toxicol. 10: 365–367, 1973.
 132. Peakall, D. B., Physiological effects of chlorinated hydrocarbons on avian species. In: Environmental Dynamics of Pesticides, edited by R. Hague and V. H. Freed. New York: Plenum Press, 1975, p. 343‐360.
 133. Peakall, D. B., J. L. Lincer, R. W. Risebrough, J. B. Pritchard, and W. B. Kinter. DDE‐induced egg‐shell thinning: Structural and physiological effects in three species. Comp. Gen. Pharmacol. 4: 305–313, 1973.
 134. Pennock, B. E., and D. E. Goldman. The action of lead and mercury on lobster axon. Federation Proc. 31: 319, 1972.
 135. Pritchard, J. B. Active transport of DDA by renal tubules in vitro. Federation Proc. 33: 514, 1974.
 136. Pritchard, J. B., Renal handling of DDA by the southern flounder. In: Pollution and Physiology of Marine Organisms, edited by F. J. Vernberg and W. B. Vernberg, New York: Academic Press, 1974, p. 165‐180.
 137. Pritchard, J. B., and W. B. Kinter. DDA: An inhibitor of chlorphenol red transport by flounder kidney in vitro. Bull. Mt. Desert Isl. Biol. Lab. 10: 67–68, 1970.
 138. Pritchard, J. B., D. B. Peakall, R. W. Risebrough, and W. B. Kinter. Eggshell thinning and enzymatic alterations in the shell gland in the white Pekin duck. Bull. Mt. Desert Isl. Biol. Lab. 12: 77–79, 1972.
 139. Rega, A. F., A. Rothstein, and R. I. Weed. Erythrocyte membrane sulfhydryl groups and the active transport of cations. J. Cellular Physiol. 70: 45–52, 1967.
 140. Renfro, J. L., B. Schmidt‐Nielsen, D. Miller, D. Benos, and J. Allen. Methyl mercury and inorganic mercury: Uptake, distribution, and effect on osmoregulatory mechanisms in fishes. In: Pollution and Physiology of Marine Organisms, edited by F. J. Vernberg and W. B. Vernberg. New York: Academic Press, 1974, p. 101‐122.
 141. Risebrough, R. W., J. Davis, and D. W. Anderson. Effects of various chlorinated hydrocarbons. In: The Biological Impact of Pesticides in the Environment, edited by J. W. Gillett. Corvallis: Oregon State Univ., 1970, p. 40‐53. (Environmental Health Sci. Ser.).
 142. Roan, C., D. Morgan, and E. H. Paschal. Urinary excretion of DDA following ingestion of DDT and DDT metabolites in man. Arch. Environ. Health. 22: 309–315, 1971.
 143. Robinson, G. W., R. A. Bradshaw, L. Kanarek, and R. L. Hill. The thiol groups of fumarase. J. Biol. Chem. 242: 2709–2718, 1967.
 144. Robinson, J. D. Structural changes in microsomal suspensions. II. Studies with brain microsomes. Arch. Biochem. Biophys. 110: 475–484, 1965.
 145. Robinson, J. D. Interaction between protein sulphydryl groups and lipid double bonds in biological membranes. Nature 212: 199–200, 1966.
 146. Ross, R. T., and F. J. Biros. Molecular complexes of 1,1,1‐trichloro‐2,2‐bis(p‐chlorophenyl)ethane with aromatic donors. Biochem. Biophys. Res. Commun. 39: 723–731, 1970.
 147. Rothstein, A. Cell membrane as site of action of heavy metals. Federation Proc. 18: 1026–1035, 1959.
 148. Rothstein, A., Sulfhydryl groups in membrane structure and function. In: Current Topics in Membranes and Transport, edited by F. Bronner and A. Kleinzeller. New York: Academic Press, 1970, vol. 1, p. 135‐176.
 149. Rothstein, A., Mercaptans, the biological targets for mercurials. In: Mercury, Mercurials and Mercaptans, edited by M. W. Miller and T. W. Clarkson. Springfield, Ill.: Thomas, 1973, p. 68‐95.
 150. Rothstein, A., M. Takeshita, and P. A. Knauf. Chemical modification of proteins involved in the permeability of the erythrocyte membrane to ions. Biomembranes 3: 393–413, 1972.
 151. Sandow, A., and A. Isaacson. Topochemical factors in potentiation of contraction by heavy metal cations. J. Gen. Physiol. 49: 937–961, 1966.
 152. Schaeffer, J. F., R. L. Preston, and P. F. Curran. Inhibition of amino acid transport in rabbit intestine by p‐chloromercuriphenyl sulfonic acid. J. Gen. Physiol. 62: 131–146, 1973.
 153. Schmidt‐Nielsen, B. Osmoregulation: effect of salinity and heavy metals. Federation Proc. 33: 2137–2146, 1974.
 154. Schneider, R. P. Regulation of sodium transport in erythrocytes. Arch. Biochem. Biophys. 160: 552–560, 1974.
 155. Schultz, S. G., and P. F. Curran. Coupled transport of sodium and organic solutes. Physiol. Rev. 50: 637–718, 1970.
 156. Scott, K. M., V. A. Knight, C. T. Settlemire, and G. P. Brierley. Differential effects of mercurial reagents on membrane thiols and on the permeability of the heart mitochondrion. Biochemistry 9: 714–724, 1970.
 157. Selwyn, M. J. Permeability effects of organomercurials. Biochem. J. 130: 65p‐67p, 1972.
 158. Settlemire, C. T., A. S. Huston, L. S. Jacobs, J. C. Havey, and J. L. Howland. Action of some insecticides on membranes of mouse liver mitochondria. Bull. Environ. Contamination Toxicol. 11: 169–173, 1974.
 159. Sha'afi, R. I., and C. M. Gary‐Bobo. Water and nonelectrolytes permeability in mammalian red cell membranes. Proc. Biophys. Mol. Biol. 26: 105–146, 1973.
 160. Sharp, C. W., D. G. Hunt, S. T. Clements, and W. E. Wilson. The influence of dichlorodiphenyltrichloroethane, polychlorinated biphenyls and anionic amphiphilic compounds on stabilization of sodium‐ and potassium‐activated adenosine triphosphatases by acidic phospholipids. Mol. Pharmacol. 10: 119–129, 1974.
 161. Sides, P. J. Effect of 2,2‐bis(p‐chlorophenyl)‐1,1,1‐trichloroethane (DDT) on toad bladder. Federation Proc. 30: 294, 1971.
 162. Sides, P. J., and A. L. Finn. Effects of 2,2‐bis(p‐chlorophenyl)‐1,1,1‐trichloroethane (DDT) on sodium transport in toad bladder. Am. J. Pathol. 70: 58a‐59a, 1973.
 163. Silbergeld, E. K., J. T. Fales, and A. M. Goldberg. Evidence for a junctional effect of lead on neuromuscular function. Nature 247: 49–50, 1974.
 164. Simon, B., R. Kinne, and G. Sachs. The presence of a HCO3‐‐ATPase in pancreatic tissue. Biochim. Biophys. Acta 282: 293–300, 1972.
 165. Sivalingan, P. M., T. Yoshida, and Y. Inada. The modes of inhibitory effects of PCB's on oxidative phosphorylation of mitochondria. Bull. Environ. Contamination Toxicol. 10: 242–247, 1973.
 166. Skou, J. C. Enzymatic basis of active transport of Na+ and K+ across cell membrane. Physiol. Rev. 45: 596–617, 1965.
 167. Smith, F. M., and J. A. Verpooret. Mg2+‐activated ATP hydrolysis and sulfhydryl groups in membranes from human erythrocytes. Can. J. Biochem. 48: 604–612, 1970.
 168. Solberg, L. A., Jr., and J. G. Forte. Differential effects of ‐SH reagents on transport and electrical properties of gastric mucosa. Am. J. Physiol. 220: 1404–1412, 1971.
 169. Somjen, G., and S. Herman. Intracellular potentials of spinal ganglion cells of rats poisoned by methyl mercury. Federation Proc. 31: 320, 1972.
 170. Southard, J. H., G. A. Blondin, and D. E. Green. Induction of transmembrane proton transfer by mercurials in mitochondria. II. Release of a Na+/K+ ionophore. J. Biol. Chem. 249: 678–681, 1974.
 171. Southard, J., P. Nitisewojo, and D. E. Green. Mercurial toxicity and the perturbation of the mitochondrial control system. Federation Proc. 33: 2147–2153, 1974.
 172. Stein, W. D. (editor)., The Movement of Molecules Across Cell Membranes. New York: Academic Press, 1967, p. 266‐308. (Theoretical and Exptl. Biol., vol. 6.).
 173. Sutherland, R. M., A. Rothstein, and R. I. Weed. Erythrocyte membrane sulfhydryl groups and cation permeability. J. Cellular Physiol. 69: 185–198, 1967.
 174. Tappel, A. L. Lipid peroxidation damage to cell components. Federation Proc. 32: 1870–1874, 1973.
 175. Taylor, T. J., F. Rieders, and J. J. Kocsis. The role of Hg++ and methyl mercury on lipid peroxidation. Federation Proc. 32: 261, 1973.
 176. Thind, G. S. Influence of propranolol on the vascular effects of cadmium and isoproterenol in rabbit aorta. Arch. Intern. Pharmacodyn. 205: 181–191, 1973.
 177. Tinsley, I. J., R. Haque, and D. Schmedding. Binding of DDT to lecithin. Science 174: 145–147, 1971.
 178. Toda, N. Influence of cadmium ions on contractile response of isolated aortas to stimulatory agents. Am. J. Physiol. 225: 350–355, 1973.
 179. Toda, N. Influence of cadmium ions on the transmembrane potential and contractility of isolated rabbit left atria. J. Pharmacol. Exptl. Therap. 186: 60‐66, 1973.
 180. Tyler, D. D. The inhibition of phosphate entry into rat liver mitochondria by organic mercurials and by formaldehyde. Biochem. J. 107: 121–123, 1968.
 181. Tyler, D. D. Evidence of a phosphate‐transporter system in the inner membrane of isolated mitochondria. Biochem. J. 111: 665–678, 1969.
 182. Ullrich, K. J., H. Fasold, S. Kloss, G. Rumrich, M. Salzer, K. Sato, B. Simon, and J. X. de Vries. Effect of SH‐, NH2‐ and COOH‐site group reagents on the transport processes in the proximal convolution of the rat kidney. Pfluegers Arch. European J. Physiol. 344: 51–68, 1973.
 183. VanSteveninck, J., R. I. Weed, and A. Rothstein. Localization of erythrocyte membrane sulfhydryl groups essential for glucose transport. J. Gen. Physiol. 48: 617–632, 1965.
 184. Van Zutphen, H., and D. G. Cornwell. Some studies on lipid peroxidation in monomolecular and bimolecular and lipid films. J. Membrane Biol. 13: 79–88, 1973.
 185. Walker, B. L., and F. A. Kummerow. Erythrocyte fatty acid composition and apparent permeability to non‐electrolytes. Proc. Soc. Exptl. Biol. Med. 115: 1099–1103, 1964.
 186. Wang, C. M., and F. Matsumura. Dieldrin, effect on ion transport activities in liver tissue. Bull. Environ. Contamination Toxicol. 4: 144–151, 1969.
 187. Wasserman, R. H., Calcium transport by selected animal cells and tissues. In: Metabolic Transport; Metabolic Pathways (3rd ed.), edited by D. M. Greenberg. New York: Academic Press, 1972, vol. 6, p. 351‐384.
 188. Watling, A. S., and M. J. Selwyn. Effect of some organometallic compounds on the permeability of chloroplast membranes. FEBS Letters 10: 139–142, 1970.
 189. Wedeen, R. P., J. K. Maesaka, M. M. Lyons, B. Weiner, G. A. Lipat, L. F. Vitale, and M. M. Joselow. Occupational lead nephropathy. Am. J. Med. 59: 630–641, 1975.
 190. Weiner, I. M., Transport of weak acids and bases. In: Handbook of Physiology. Renal Physiology, edited by J. Orloff and R. W. Berliner. Washington, D.C.: Am. Physiol. Soc., 1973, sect. 8, chapt. 17, p. 521‐554.
 191. Weisbart, M., and D. Fewer. Sublethal effect of DDT on osmotic and ionic regulation by the goldfish Carassius auratus. Can. J. Zool. 52: 739–744, 1974.
 192. Wells, M. R., J. B. Phillips, and G. G. Murphy. ATPase activity in tissues of the map turtle, Graptemys geographica, following in vitro treatment with aldrin and dieldrin. Bull. Environ. Contamination Toxicol. 11: 572–576, 1973.
 193. Wells, M. R., and J. D. Yarbrough. Retention of 14C‐DDT in cellular fractions of vertebrate insecticide‐resistant and susceptible fish. Toxicol. Appl. Pharmacol. 22: 409–414, 1972.
 194. White, J. F., and A. Rothstein. The interaction of methyl mercury with erythrocytes. Toxicol. Appl. Pharmacol. 26: 370–384, 1973.
 195. Wilson, N. K., and W. E. Wilson. Complex equilibria involving DDT and model compounds for phospholipid and protein. Sci. Total Environ. 1: 245–251, 1972.
 196. Wilson, W. E., L. Fishbein, and S. T. Clements. DDT: Participation in ultraviolet‐detectable, charge‐transfer complexation. Science 171: 180–182, 1971.
 197. Wizeman, V., I. Schultz, and B. Simon. SH‐groups in the surface of pancreas cells involved in secretin stimulation and glucose‐mediated secretion. Biochim. Biophys. Acta 307: 366–371, 1973.
 198. Wurster, C. F., Jr.. DDT reduces photosynthesis by marine phytoplankton. Science 159: 1474–1475, 1968.
 199. Yap, H. H., and L. K. Cutkomp. Activity and rhythm of ATPases in larvae of the mosquito, Aedes aegypti L. Life Sci. Part 2 9: 1419‐1425, 1970.
 200. Yap, H. H., D. Desaiah, L. K. Cutkomp, and R. B. Koch. Sensitivity of fish ATPases to polychlorinated biphenyls. Nature 233: 61–62, 1971.
 201. Yarbrough, J. D., and M. R. Wells. Vertebrate insecticide resistance: The in vitro endrin effect on succinic dehydrogenase activity on endrin‐resistant and susceptible mosquito‐fish. Bull. Environ. Contamination Toxicol. 6: 171–176, 1971.
 202. Yariv, J., A. J. Kalb, E. Katchalski, R. Goldman, and E. W. Thomas. Two locations of the lac permease sulfhydryl in the membrane of E. coli. FEBS Letters 5: 173‐176, 1969.

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Article Title: Altered Permeability of Cell Membranes
 

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W. B. Kinter, J. B. Pritchard. Altered Permeability of Cell Membranes. Compr Physiol 2011, Supplement 26: Handbook of Physiology, Reactions to Environmental Agents: 563-576. First published in print 1977. doi: 10.1002/cphy.cp090136