Summary
Effects of a potent synthetic glucocorticoid, methylprednisolone (MP), on transepithelial Na transport were examined in rabbit descending colon. Current-voltage (I–V) relations of the amiloride-sensitive apical Na entry pathway were measured in colonic tissues of control and MP-treated (40 mg im for 2 days) animals. Tissues were bathed mucosally by solutions of various Na activities, (Na)m, ranging from 6.2 to 75.6mm, and serosally by a high K solution. TheseI–V relations conformed to the “constant field” flux equation permitting determination of the permeability of the apical membrane to Na,P mNa , and the intracellular Na activity, (Na)c. The following empirical relations were observed for both control and MP-treated tissues: (i) Na transport increases hyperbolically with increasing (Na)m obeying simple Michaelis-Mentin kinetics; (ii)P mNa decreased hyperbolically with increasing (Na)m, but was unrelated to individual variations in (Na)c; (iii) (Na)c increased hyperbolically with (Na)m; (iv) both spontaneous and steroid-stimulated variations in Na entry rate could be attributed entirely to parallel variations inP mNa at each mucosal Na activity. Comparison of these empirical, kinetic relations between control and MP-treated tissues revealed: (i) maximal Na current andP mNa were greater in MP tissues, but the (Na)m's at which current andP mNa were half-maximal were markedly reduced; (ii) (Na)c was significantly increased in MP tissues at each (Na)m while the (Na)m at half-maximal (Na)c was unchanged. These results provide direct evidence that glucocorticoids cause marked stimulation of Na absorption across rabbit colon primarily by increasing the Na permeability of the apical membrane. While the mechanism for the increased permeability remains to be determined, the altered relation betweenP mNa and (Na)m suggests possible differences in the conformation or environment of the Na channel in MP-treated tissues.
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Bastl, C.P., Barnett, C.A., Schmidt, T.J., Litwack, G. 1984. Glucocorticoid stimulation of sodium absorption in colonic epithelia is mediated by corticosteroid IB receptor.J. Biol. Chem. 259:1186–1195
Bastl, C.P., Binder, H.J., Hayslett, J.P. 1980. Role of glucocorticoids and aldosterone in maintenance of colonic cation transport.Am. J. Physiol. 238:F181-F186
Charney, A.N., Kinsey, M.D., Meyers, L., Gianella, R.A., Gots, R.E. 1975. Na−K-activated adenosine triphosphatase and intestinal electrolyte transport: Effect of adrenal steroids.J. Clin. Invest. 56:653–660
Charney, A.N., Wallach, J., Ceccarelli, S., Donowitz, M., Costenbader, C.L. 1981. Effects of spironolactone and amiloride on corticosteroid-induced changes in colonic function.Am. J. Physiol. 241:G300-G305
Clauss, W., Durr, J., Skadhauge, E., Hornicke, H. 1985. Effects of aldosterone and dexamethasone on apical membrane properties and Na-transport of rabbit distal colon in vitro.Pfluegers Arch. 403:186–192
Cuthbert, A.W., Edwardson, J.M., Bindsley, N., Skadhauge, E. 1982. Identification of potential components of the transport mechanism for Na+ in the hen colon and coprodaeum.Pfluegers Arch. Gesamte Physiol. 392:347–351
Davis, C.W., Finn, A.L. 1982. Sodium transport inhibition by amiloride reduces basolateral membrane potassium conductance in tight epithelia.Science 216:525–527
DeLong, J., Civan, M.M. 1984. Apical sodium entry in split frog skin: Current-voltage relationship.J. Membrane Biol. 82:25–40
Eaton, D.C. 1981. Intracellular sodium ion activity and sodium transport in rabbit urinary bladder.J. Physiol. (London) 316:527–544
Eaton, D.C., Frace, A.M., Silverthorn, S.U. 1982. Active and passive Na+ fluxes across the basolateral membrane of rabbit urinary bladder.J. Membrane Biol. 67:219–229
Frizzell, R.A., Koch, M.J., Schultz, S.G. 1976. Ion transport by rabbit colon: I. Active and passive components.J. Membrane Biol. 27:297–316
Frizzell, R.A., Schultz, S.G. 1978. Effect of aldosterone on ion transport by rabbit colonin vitro.J. Membrane Biol. 39:1–26
Fuchs, W., Larsen, E.H., Lindemann, B. 1977. Current-voltage curve of sodium channels and concentration dependence of sodium permeability in frog skin.J. Physiol. (London) 267:137–166
Garty, H., Edelman, I.S. 1983. Amiloride-sensitive trypsinization of apical sodium channels. Analysis of hormonal regulation of sodium transport in toad bladder.J. Gen. Physiol. 81:785–803
Goldman, D. 1943. Potential, impedance and rectification in membranes.J. Gen. Physiol. 27:37–60
Halm, D.R., Dawson, D.C. 1983. Cation activation of the basolateral sodium-potassium pump in turtle colon.J. Gen. Physiol. 82:315–329
Hodgkin, A.L., Katz, B. 1949. The effect of sodium ions on the electrical activity of the giant axon of the squid.J. Physiol. (London) 108:37–77
Hudson, R.L., Schultz, S.G. 1984. Sodium-coupled sugar transport: Effects on intracellular sodium activities and sodiumpump activity.Science 224:1237–1239
Klemperer, G., Garcia-Diaz, J.F., Essig, A. 1984. Effects of high serosal K concentrations on electrophysiological parameters of frog skin.J. Gen. Physiol. 84:29a
Lewis, S.A. 1983. Control of Na+ and water absorption across vertebrate “tight” epithelia by ADH and aldosterone.J. Exp. Biol. 106:9–24
Lewis, S.A., DeMoura, J.L.C. 1984. Incorporation of cytoplasmic vesicles into apical membrane of mammalian urinary bladder.Nature (London) 297:685–688
Lewis, S.A., Eaton, D.C., Diamond, J.M. 1976. The mechanism, of Na+ transport by rabbit urinary bladder.J. Membrane Biol. 28:41–70
Lewis, S.A., Hanrahan, J.W., Van Driessche, W. 1984. Channels across epithelial cell layers.In: Current Topics in Membranes and Transport, W.D. Stein, editor. Vol. 21, pp. 253–293 Academic, New York
Lewis, S.A., Wills, N.K. 1983. Apical membrane permeability and kinetic properties of the sodium pump in rabbit urinary bladder.J. Physiol. (London) 341:169–184
Lewis, S.A., Wills, N.K., Eaton, D.C. 1978. Basolateral membrane potential of a tight epithelium: Ionic diffusion and electrogenic pumps.J. Membrane Biol. 41:117–148
Loo, D.D.F., Lewis, S.A., Ifshin, M.S., Diamond, J.M. 1983. Turnover membrane insertion and degradation of sodium channels in rabbit urinary bladder.Science 221:1288–1290
Marver, D. 1984. Assessment of mineralocorticoid activity in the rabbit colon.Am. J. Physiol. 246:F437-F446
Nagel, W. 1977. Effect of high K upon the frog skin intracellular potential.Pfluegers Arch. 369:R22
Nagel, W., Garcia-Diaz, J.F., Essig, A. 1983. Contribution of junctional conductance to the cellular voltage-divider ratio in frog skins.Pfluegers Arch. 399:336–341
Nielsen, R. 1979. Coupled transepithelial sodium and potassium transport across isolated frog skin: Effect of oubain, amiloride, and the polyene antibiotic filipin.J. Membrane Biol. 51:161–184
O'Neil, R.G. 1986. Adrenal steroid regulation of potassium transport.In: Potassium: Physiology and Pathophysiology. G. Giebisch, editor. Academic, New York (in press)
O'Neil, R.G., Hayhurst, R.A. 1985. Sodium-dependent modulation of the renal Na−K-ATPase: Influence of mineralocorticoids on the cortical collecting duct.J. Membrane Biol. 85:169–179
Palmer, L.G. 1984. Use of potassium depolarization to study apical transport properties in epithelia.In: Current Topics in Membranes and Transport. J.B. Wade and S.A. Lewis, editors. Vol. 20, pp. 105–121. Academic, New York
Palmer, L.G. 1985. Modulation of apical Na permeability of the toad urinary bladder by intracellular Na, Ca and H.J. Membrane Biol. 83:57–69
Palmer, L.G., Edelman, I.S. 1981. Control of apical sodium permeability in the toad urinary bladder by aldosterone.Ann. N.Y. Acad. Sci. 372:1–14
Palmer, L.G., Edelman, I.S., Lindemann, B. 1980. Current-voltage analysis of apical sodium transport in toad urinary bladder: Effects of inhibitors of transport and metabolism.J. Membrane Biol. 57:59–71
Palmer, L.G., Li, J.H.-Y., Lindemann, B., Edelman, I. 1982. Aldosterone control of the density of sodium channels in the toad urinary bladder.J. Membrane Biol. 64:91–102
Petty, K.J., Kokko, J.P., Marver, D. 1981. Secondary effect of aldosterone on Na−K ATPase activity in the rabbit cortical collecting tubule.J. Clin. Invest. 68:1514–1521
Reuss, L., Lewis, S.A., Wills, N.K., Helman, S.I., Cox, T.C., Boron, W.F., Siebens, A.W., Guggino, W.B., Giebisch, G., Schultz, S.G. 1984. Ion transport processes in basolateral membranes of epithelia.Fed. Proc. 43:2488–2502
Sansom, S.C., O'Neil, R.G. 1985. Mineralocorticoid regulation of apical cell membrane Na+ and K+ transport of the cortical collecting duct.Am. J. Physiol. 248:F858-F868
Sansom, S.C., O'Neil, R.G. 1986. Effects of mineralocorticoids on active and passive transport properties of the basolateral membrane of the cortical collecting duct.Am. J. Physiol. (in Press)
Schultz, S.G. 1985. Regulatory mechanisms in sodium-absorbing epithelia.In: The Kidney: Physiology and Pathophysiology. D.W. Seldin and G. Giebisch, editors. Ch. 10, pp. 189–198 Raven, New York.
Segel, I.H. 1975. Enzyme Kinetics. John Wiley & Sons, New York
Sellin, J.H., Desoigne, R.C. 1983. Methylprednisolone increases absorptive capacity in rabbit ileumin vitro.Am. J. Physiol. 245:G562-G567
Sellin, J.H., Desoigne, R.C. 1985. Steroids alter ion transport and absorptive capacity in proximal and distal colon.Am. J. Physiol. 249:G113-G119
Tang, J., Abramcheck, F.J., VanDrissche, W., Helman, S.I. 1985. Electrophysiology and noise analysis of K+-depolarized epithelia of frog skin.Am. J. Physiol. 249:C421-C429
Taylor, A. 1981. Role of cytosolic calcium and sodium-calcium exchange in regulation of transepithelial sodium and water absorption.In: Ion Transport by Epithelia. S.G. Schultz, editor. pp. 233–259. Raven, New York
Thomas, S.R., Suzuki, Y., Thompson, S.M., Schultz, S.G. 1983. Electrophysiology ofNecturus urinary bladder: I. “Instantaneous” current-voltage relations in the presence of varying mucosal sodium concentrations.J. Membrane Biol. 73:157–175
Thompson, S.M. 1986a. Relations between chord and slope conductances and equivalent electromotive forces.Am. J. Physiol. 250:C333-C339
Thompson, S.M. 1986b. Differential effects of amiloride on aldosterone and methylprednisolone (MP) stimulation of sodium permeability in rabbit distal colon.Fed. Proc. (in press)
Thompson, S.M., Sellin, J.H. 1984. Effects of methylprednisolone on Na transport in rabbit colon.Fed. Proc. 43:1086
Thompson, S.M., Suzuki, Y., Schultz, S.G. 1982a. The electrophysiology of rabbit descending colon: I. Instantaneous transepithelial current-voltage relations and the current-voltage relations of the Na-entry mechanism.J. Membrane Biol. 66:41–54
Thompson, S.M., Suzuki, Y., Schultz, S.G. 1982b. The electrophysiology of rabbit descending colon: II. Current-voltage relations of the apical membrane, the basolateral membrane, and the parallel pathways.J. Membrane Biol. 66:55–61
Turnheim, K., Frizzell, R.A., Schultz, S.G. 1978. Interaction between cell sodium and the amiloride-sensitive sodium entry step in rabbit colon.J. Membrane Biol. 39:233–256
Turnheim, K., Hudson, R.L., Schultz, S.G. 1986. Effect of Na deprivation on intracellular Na activity in descending rabbit colon.Biochim. Biophys. Acta (submitted)
Turnheim, K., Thompson, S.M., Schultz, S.G. 1983. Relation between intracellular sodium and active sodium transport in rabbit colon: Current-voltage relations of the apical sodium entry mechanisms in the presence of varying luminal sodium concentrations.J. Membrane Biol. 76:299–309
Van Driessche, W., Lindemann, B. 1979. Concentration dependence of currents through single sodium-selective pores in frog skin.Nature (London) 282:519–520
Will, P.C., DeLisle, R.C., Cortright, R.N., Hopfer, U. 1981. Induction of amiloride-sensitive sodium transport in the intestines by adrenal steroids.Ann. N.Y. Acad. Sci. 372:64–76
Wills, N.K., Lewis, S.A., Eaton, D.C. 1979. Active and passive properties of rabbit descending colon: A microelectrode and nystatin study.J. Membrane Biol. 45:81–108
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Thompson, S.M., Sellin, J.H. Relationships among sodium current, permeability, and Na activities in control and glucocorticoid-stimulated rabbit descending colon. J. Membrain Biol. 92, 121–134 (1986). https://doi.org/10.1007/BF01870702
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DOI: https://doi.org/10.1007/BF01870702