Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Aug;80(2):348–356. doi: 10.1172/JCI113079

Regulation of cation transport by low doses of glucocorticoids in in vivo adrenalectomized rat colon.

C P Bastl
PMCID: PMC442244  PMID: 2956277

Abstract

A dose response curve for glucocorticoid-induced proximal and distal colonic cation transport in vivo was established in adrenalectomized rats. All doses (0.5-50 nmol/100 g body wt) stimulated sodium absorption. Distal sodium absorption did not saturate at dexamethasone levels that saturate the glucocorticoid receptor but also bind to greater than 35% of aldosterone receptors. Saturation of the pure glucocorticoid response occurred in both segments with RU26988, a synthetic glucocorticoid that does not occupy aldosterone receptors. Maximum velocities for pure glucocorticoid-induced sodium absorption were 15 and 16 mu eq/min per g dry tissue, and Michaelis constants (Km) were 4.2 and 4.6 X 10(-9) mol/liter for proximal and distal colon. Kms are similar to the dissociation constant for the colonic glucocorticoid receptor and too low for significant aldosterone receptor occupancy. Dexamethasone increased sodium absorption significantly within 30 min of injection, suggesting the response is not dependent on new protein synthesis. Similar time and dose responses in proximal and distal colon suggest glucocorticoids stimulate the same pathway in both segments.

Full text

PDF
348

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bastl C. P., Barnett C. A., Schmidt T. J., Litwack G. Glucocorticoid stimulation of sodium absorption in colon epithelia is mediated by corticosteroid IB receptor. J Biol Chem. 1984 Jan 25;259(2):1186–1195. [PubMed] [Google Scholar]
  2. Bastl C. P., Binder H. J., Hayslett J. P. Role of glucocorticoids and aldosterone in maintenance of colonic cation transport. Am J Physiol. 1980 Mar;238(3):F181–F186. doi: 10.1152/ajprenal.1980.238.3.F181. [DOI] [PubMed] [Google Scholar]
  3. Binder H. J. Effect of dexamethasone on electrolyte transport in the large intestine of the rat. Gastroenterology. 1978 Aug;75(2):212–217. [PubMed] [Google Scholar]
  4. Bridges R. J., Rummel W., Wollenberg P. Effects of vasopressin on electrolyte transport across isolated colon from normal and dexamethasone-treated rats. J Physiol. 1984 Oct;355:11–23. doi: 10.1113/jphysiol.1984.sp015402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Charney A. N., Kinsey M. D., Myers L., Gainnella R. A., Gots R. E. Na+-K+-activated adenosine triphosphatase and intestinal electrolyte transport. Effect of adrenal steroids. J Clin Invest. 1975 Sep;56(3):653–660. doi: 10.1172/JCI108135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Charney A. N., Wallach J., Ceccarelli S., Donowitz M., Costenbader C. L. Effects of spironolactone and amiloride on corticosteroid-induced changes in colonic function. Am J Physiol. 1981 Oct;241(4):G300–G305. doi: 10.1152/ajpgi.1981.241.4.G300. [DOI] [PubMed] [Google Scholar]
  7. Claire M., Steimer J. L., Oblin M. E., Gaeggeler H. P., Venot A., Corvol P., Rossier B. C. Cytoplasmic and nuclear uptake of aldosterone in toad bladder: a mathematical modeling approach. Am J Physiol. 1985 Jan;248(1 Pt 1):C88–101. doi: 10.1152/ajpcell.1985.248.1.C88. [DOI] [PubMed] [Google Scholar]
  8. Clauss W., Dürr J., Skadhauge E., Hörnicke H. Effects of aldosterone and dexamethasone on apical membrane properties and Na-transport of rabbit distal colon in vitro. Pflugers Arch. 1985 Feb;403(2):186–192. doi: 10.1007/BF00584098. [DOI] [PubMed] [Google Scholar]
  9. Clauss W., Schäfer H., Horch I., Hörnicke H. Segmental differences in electrical properties and Na-transport of rabbit caecum, proximal and distal colon in vitro. Pflugers Arch. 1985 Mar;403(3):278–282. doi: 10.1007/BF00583600. [DOI] [PubMed] [Google Scholar]
  10. D'Agostino J., Vaeth G. F., Henning S. J. Diurnal rhythm of total and free concentrations of serum corticosterone in the rat. Acta Endocrinol (Copenh) 1982 May;100(1):85–90. doi: 10.1530/acta.0.1000085. [DOI] [PubMed] [Google Scholar]
  11. Dolman D., Edmonds C. J. The effect of aldosterone and the renin-angiotensin system on sodium, potassium and chloride transport by proximal and distal rat colon in vivo. J Physiol. 1975 Sep;250(3):597–611. doi: 10.1113/jphysiol.1975.sp011072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Edelman I. S. Mechanism of action of steroid hormones. J Steroid Biochem. 1975 Mar-Apr;6(3-4):147–159. doi: 10.1016/0022-4731(75)90125-9. [DOI] [PubMed] [Google Scholar]
  13. Edmonds C. J. Amiloride sensitivity of the transepithelial electrical potential and of sodium and potassium transport in rat distal colon in vivo. J Physiol. 1981;313:547–559. doi: 10.1113/jphysiol.1981.sp013681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Edmonds C. J., Marriott J. C. The effect of aldosterone and adrenalectomy on the electrical potential difference of rat colon and on the transport of sodium, potassium, chloride and bicarbonate. J Endocrinol. 1967 Dec;39(4):517–531. doi: 10.1677/joe.0.0390517. [DOI] [PubMed] [Google Scholar]
  15. Edmonds C. J., Marriott J. Factors influencing the electrical potential across the mucosa of rat colon. J Physiol. 1968 Feb;194(2):457–478. doi: 10.1113/jphysiol.1968.sp008418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Edmonds C. J. The gradient of electrical potential difference and of sodium and potassium of the gut contents along the caecum and colon of normal and sodium-depleted rats. J Physiol. 1967 Dec;193(3):571–588. doi: 10.1113/jphysiol.1967.sp008379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Edmonds C. J. Transport of potassium by the colon of normal and sodium-depleted rats. J Physiol. 1967 Dec;193(3):603–617. doi: 10.1113/jphysiol.1967.sp008381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Firestone G. L., Payvar F., Yamamoto K. R. Glucocorticoid regulation of protein processing and compartmentalization. Nature. 1982 Nov 18;300(5889):221–225. doi: 10.1038/300221a0. [DOI] [PubMed] [Google Scholar]
  19. Foster E. S., Hayslett J. P., Binder H. J. Mechanism of active potassium absorption and secretion in the rat colon. Am J Physiol. 1984 May;246(5 Pt 1):G611–G617. doi: 10.1152/ajpgi.1984.246.5.G611. [DOI] [PubMed] [Google Scholar]
  20. Foster E. S., Zimmerman T. W., Hayslett J. P., Binder H. J. Corticosteroid alteration of active electrolyte transport in rat distal colon. Am J Physiol. 1983 Nov;245(5 Pt 1):G668–G675. doi: 10.1152/ajpgi.1983.245.5.G668. [DOI] [PubMed] [Google Scholar]
  21. Frizzell R. A., Koch M. J., Schultz S. G. Ion transport by rabbit colon. I. Active and passive components. J Membr Biol. 1976;27(3):297–316. doi: 10.1007/BF01869142. [DOI] [PubMed] [Google Scholar]
  22. Frizzell R. A., Schultz S. G. Effect of aldosterone on ion transport by rabbit colon in vitro. J Membr Biol. 1978 Feb 6;39(1):1–26. doi: 10.1007/BF01872752. [DOI] [PubMed] [Google Scholar]
  23. Fromm M., Hegel U. Segmental heterogeneity of epithelial transport in rat large intestine. Pflugers Arch. 1978 Dec 15;378(1):71–83. doi: 10.1007/BF00581960. [DOI] [PubMed] [Google Scholar]
  24. Fromm M., Oelkers W., Hegel U. Time course of aldosterone and corticosterone plasma levels in rats during general anaesthesia and abdominal surgery. Pflugers Arch. 1983 Dec;399(4):249–254. doi: 10.1007/BF00652747. [DOI] [PubMed] [Google Scholar]
  25. Geering K., Claire M., Gaeggeler H. P., Rossier B. C. Receptor occupancy vs. induction of Na+-K+-ATPase and Na+ transport by aldosterone. Am J Physiol. 1985 Jan;248(1 Pt 1):C102–C108. doi: 10.1152/ajpcell.1985.248.1.C102. [DOI] [PubMed] [Google Scholar]
  26. Gomez-Sanchez C. E., Gomez-Sanchez E. P. RU-26988--a new tool for the study of the mineralocorticoid receptor. Endocrinology. 1983 Sep;113(3):1004–1009. doi: 10.1210/endo-113-3-1004. [DOI] [PubMed] [Google Scholar]
  27. Hayslett J. P., Halevy J., Pace P. E., Binder H. J. Demonstration of net potassium absorption in mammalian colon. Am J Physiol. 1982 Mar;242(3):G209–G214. doi: 10.1152/ajpgi.1982.242.3.G209. [DOI] [PubMed] [Google Scholar]
  28. Hirsch D., Pace P., Binder H. J., Hayslett J. P. Evidence that aldosterone influences transport in target tissues by dissimilar mechanisms. Am J Physiol. 1985 Apr;248(4 Pt 2):F507–F512. doi: 10.1152/ajprenal.1985.248.4.F507. [DOI] [PubMed] [Google Scholar]
  29. Horster M., Lückhoff A. Aldosterone on sodium transport of rat distal colon in long-term adrenalectomy during acute and chronic substitution. J Physiol. 1983 Jul;340:503–511. doi: 10.1113/jphysiol.1983.sp014776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Jorkasky D., Cox M., Feldman G. M. Differential effects of corticosteroids on Na+ transport in rat distal colon in vitro. Am J Physiol. 1985 Apr;248(4 Pt 1):G424–G431. doi: 10.1152/ajpgi.1985.248.4.G424. [DOI] [PubMed] [Google Scholar]
  31. Lan N. C., Graham B., Bartter F. C., Baxter J. D. Binding of steroids to mineralocorticoid receptors: implications for in vivo occupancy by glucocorticoids. J Clin Endocrinol Metab. 1982 Feb;54(2):332–342. doi: 10.1210/jcem-54-2-332. [DOI] [PubMed] [Google Scholar]
  32. Martin R. S., Jones W. J., Hayslett J. P. Animal model to study the effect of adrenal hormones on epithelial function. Kidney Int. 1983 Sep;24(3):386–391. doi: 10.1038/ki.1983.171. [DOI] [PubMed] [Google Scholar]
  33. Marusic E. T., Hayslett J. P., Binder H. J. Corticosteroid-binding studies in cytosol of colonic mucosa of the rat. Am J Physiol. 1981 Jun;240(6):G417–G423. doi: 10.1152/ajpgi.1981.240.6.G417. [DOI] [PubMed] [Google Scholar]
  34. Marver D. Assessment of mineralocorticoid activity in the rabbit colon. Am J Physiol. 1984 Apr;246(4 Pt 2):F437–F446. doi: 10.1152/ajprenal.1984.246.4.F437. [DOI] [PubMed] [Google Scholar]
  35. Moguilewsky M., Raynaud J. P. Evidence for a specific mineralocorticoid receptor in rat pituitary and brain. J Steroid Biochem. 1980 Jan;12:309–314. doi: 10.1016/0022-4731(80)90285-x. [DOI] [PubMed] [Google Scholar]
  36. Perrone R. D., Jenks S. L. Suppression of coupled Na-Cl absorption by aldosterone and dexamethasone in rat distal colon in vitro. Am J Physiol. 1984 Jun;246(6 Pt 2):F785–F793. doi: 10.1152/ajprenal.1984.246.6.F785. [DOI] [PubMed] [Google Scholar]
  37. Rafestin-Oblin M. E., Lombes M., Michiel J. B., Michaud A., Claire M. Mineralocorticoid receptors in the epithelial cells of human colon and ileum. J Steroid Biochem. 1984 Jan;20(1):311–315. doi: 10.1016/0022-4731(84)90223-1. [DOI] [PubMed] [Google Scholar]
  38. Rask-Madsen J. Transepithelial ionic transport and electrical polarization in the large bowel. Scand J Gastroenterol. 1974;9(3):223–229. [PubMed] [Google Scholar]
  39. Rousseau G. G., Baxter J. D., Tomkins G. M. Glucocorticoid receptors: relations between steroid binding and biological effects. J Mol Biol. 1972 Jun 14;67(1):99–115. doi: 10.1016/0022-2836(72)90389-0. [DOI] [PubMed] [Google Scholar]
  40. Sandle G. I., Hayslett J. P., Binder H. J. Effect of chronic hyperaldosteronism on the electrophysiology of rat distal colon. Pflugers Arch. 1984 May;401(1):22–26. doi: 10.1007/BF00581528. [DOI] [PubMed] [Google Scholar]
  41. Schulman G., Miller-Diener A., Litwack G., Bastl C. P. Characterization of the rat colonic aldosterone receptor and its activation process. J Biol Chem. 1986 Sep 15;261(26):12102–12108. [PubMed] [Google Scholar]
  42. Schultz S. G., Frizzell R. A., Nellans H. N. Active sodium transport and the electrophysiology of rabbit colon. J Membr Biol. 1977 May 12;33(3-4):351–384. doi: 10.1007/BF01869524. [DOI] [PubMed] [Google Scholar]
  43. Sellin J. H., DeSoignie R. C. Methylprednisolone increases absorptive capacity of rabbit ileum in vitro. Am J Physiol. 1983 Oct;245(4):G562–G567. doi: 10.1152/ajpgi.1983.245.4.G562. [DOI] [PubMed] [Google Scholar]
  44. Sellin J. H., DeSoignie R. Rabbit proximal colon: a distinct transport epithelium. Am J Physiol. 1984 May;246(5 Pt 1):G603–G610. doi: 10.1152/ajpgi.1984.246.5.G603. [DOI] [PubMed] [Google Scholar]
  45. Sellin J. H., Field M. Physiologic and pharmacologic effects of glucocorticoids on ion transport across rabbit ileal mucosa in vitro. J Clin Invest. 1981 Mar;67(3):770–778. doi: 10.1172/JCI110094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Smith P. L., McCabe R. D. Mechanism and regulation of transcellular potassium transport by the colon. Am J Physiol. 1984 Nov;247(5 Pt 1):G445–G456. doi: 10.1152/ajpgi.1984.247.5.G445. [DOI] [PubMed] [Google Scholar]
  47. Tai Y. H., Decker R. A., Marnane W. G., Charney A. N., Donowitz M. Effects of methylprednisolone on electrolyte transport by in vitro rat ileum. Am J Physiol. 1981 May;240(5):G365–G370. doi: 10.1152/ajpgi.1981.240.5.G365. [DOI] [PubMed] [Google Scholar]
  48. Teutsch G., Costerousse G., Deraedt R., Benzoni J., Fortin M., Philibert D. 17 alpha-alkynyl-11 beta, 17-dihydroxyandrostane derivatives : a new class of potent glucocorticoids. Steroids. 1981 Dec;38(6):651–665. doi: 10.1016/0039-128x(81)90084-2. [DOI] [PubMed] [Google Scholar]
  49. Warnock D. G., Edelman I. S. Occupancy of aldosterone binding sites in rat kidney cytosol. Mol Cell Endocrinol. 1978 Nov;12(2):221–233. doi: 10.1016/0303-7207(78)90116-8. [DOI] [PubMed] [Google Scholar]
  50. Will P. C., Cortright R. N., DeLisle R. C., Douglas J. G., Hopfer U. Regulation of amiloride-sensitive electrogenic sodium transport in the rat colon by steroid hormones. Am J Physiol. 1985 Jan;248(1 Pt 1):G124–G132. doi: 10.1152/ajpgi.1985.248.1.G124. [DOI] [PubMed] [Google Scholar]
  51. Will P. C., Cortright R. N., Groseclose R. G., Hopfer U. Amiloride-sensitive salt and fluid absorption in small intestine of sodium-depleted rats. Am J Physiol. 1985 Jan;248(1 Pt 1):G133–G141. doi: 10.1152/ajpgi.1985.248.1.G133. [DOI] [PubMed] [Google Scholar]
  52. Will P. C., DeLisle R. C., Cortright R. N., Hopfer U. Induction of amiloride-sensitive sodium transport in the intestines by adrenal steroids. Ann N Y Acad Sci. 1981;372:64–78. doi: 10.1111/j.1749-6632.1981.tb15458.x. [DOI] [PubMed] [Google Scholar]
  53. Will P. C., Lebowitz J. L., Hopfer U. Induction of amiloride-sensitive sodium transport in the rat colon by mineralocorticoids. Am J Physiol. 1980 Apr;238(4):F261–F268. doi: 10.1152/ajprenal.1980.238.4.F261. [DOI] [PubMed] [Google Scholar]
  54. Yau W. M., Makhlouf G. M. Comparison of transport mechanisms in isolated ascending and descending rat colon. Am J Physiol. 1975 Jan;228(1):191–195. doi: 10.1152/ajplegacy.1975.228.1.191. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES