• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Mar 1981; 67(3): 770–778.
PMCID: PMC370628

Physiologic and Pharmacologic Effects of Glucocorticoids on Ion Transport across Rabbit Ileal Mucosa In Vitro

Abstract

Physiologic and pharmacologic effects of glucocorticoids on ileal ion transport were examined in vitro. Tissues were obtained from the three following groups of rabbits: (a) normal; (b) glucocorticoid deficient, which were treated with aminoglutethimide (AG), 100 mg twice daily for 3 d, with a resulting marked reduction in urinary cortisol excretion but no decrease in urinary aldosterone; and (c) methylprednisolone-treated (MP), 40 mg daily for 2 d. Transileal NaCl fluxes were measured with radioisotopes under short-circuit conditions, and the net HCO3 flux was assumed equal to that portion of the short-circuit current (Isc) not accounted for by Na and Cl. In NaCl Ringer's solution containing 25 mM HCO3 (pH 7.4), normals absorbed both Na and Cl and secreted HCO3; the Isc was greater in both AG and MP groups than in normals; in the AG group, no Na was absorbed, and Cl as well as HCO3 was secreted; in the MP group, more Na was absorbed and more HCO3 secreted than in normals. Addition of glucose to the luminal side caused similar increments in Isc in all three groups, suggesting similar rates of Na-coupled glucose absorption. Secretory response was assessed with a maximal secretory simulus (8-Br-cAMP) and also a submaximal, cGMP-related secretory stimulus (Escherichia coli heat-stable enterotoxin). After addition of 8-Br-cAMP, the rates of net Cl secretion were similar in all three groups, suggesting no effect of glucocorticoids on maximal secretory capacity. Because the AG group was already secreting Cl, however, the cAMP-induced change in net Cl flux was least in this group. After addition of heat-stable enterotoxin, there were similar changes in net Cl flux in all three groups. To examine specifically Cl-independent, electrogenic Na transport, we used a 10 mM HCO3, Cl-free SO4-Ringer (ph 7.2) in which net Na absorption was previously shown to be equal to the Isc. Under these conditions, Isc was greatest in the MP group and least in the AG group. In vitro addition of hydrocortisone, 50 μg/ml, to AG tissues had no effect on Cl fluxes or Isc over a 3.5-h period. No differences among groups were observed with respect to morphology, electrical resistance, or cGMP concentration. We conclude that (a) the effect of glucocorticoid deficiency is similar to that of a submaximal secretory stimulus in that Na absorption is inhibited and some Cl secretion develops; (b) electrogenic Na absorption is depressed in glucocorticoid deficiency and enhanced in glucocorticoid excess; (c) glucocorticoid excess increases HCO3 secretion; and (d) glucocorticoid status does not affect maximal secretory capacity.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Frizzell RA, Schultz SG. Effect of aldosterone on ion transport by rabbit colon in vitro. J Membr Biol. 1978 Feb 6;39(1):1–26. [PubMed]
  • Edmonds CJ, Marriott JC. 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. [PubMed]
  • WELBOURN RB. DIARRHOEA OF SMALL BOWEL ORIGIN. ENDOCRINE CAUSES OF DIARRHOEA. Proc R Soc Med. 1963 Dec;56:1080–1081. [PMC free article] [PubMed]
  • Field M, Fromm D, McColl I. Ion transport in rabbit ileal mucosa. I. Na and Cl fluxes and short-circuit current. Am J Physiol. 1971 May;220(5):1388–1396. [PubMed]
  • Harper JF, Brooker G. Femtomole sensitive radioimmunoassay for cyclic AMP and cyclic GMP after 2'0 acetylation by acetic anhydride in aqueous solution. J Cyclic Nucleotide Res. 1975;1(4):207–218. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Murphy BE. Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding radioassay. J Clin Endocrinol Metab. 1967 Jul;27(7):973–990. [PubMed]
  • Mayes D, Furuyama S, Kem DC, Nugent CA. A radioimmunoassay for plasma aldosterone. J Clin Endocrinol Metab. 1970 May;30(5):682–685. [PubMed]
  • Field M, Graf LH, Jr, Laird WJ, Smith PL. Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2800–2804. [PMC free article] [PubMed]
  • Dexter RN, Fishman LM, Ney RL, Liddle GW. Inhibition of adrenal corticosteroid synthesis by aminoglutethimide: studies of the mechanism of action. J Clin Endocrinol Metab. 1967 Apr;27(4):473–480. [PubMed]
  • Fishman LM, Liddle GW, Island DP, Fleischer N, Küchel O. Effects of amino-glutethimide on adrenal function in man. J Clin Endocrinol Metab. 1967 Apr;27(4):481–490. [PubMed]
  • Dietz J, Field M. Ion transport in rabbit ileal mucosa. IV. Bicarbonate secretion. Am J Physiol. 1973 Oct;225(4):858–861. [PubMed]
  • Sheerin HE, Field M. Ileal HCO3 secretion: relationship to Na and Cl transport and effect of theophylline. Am J Physiol. 1975 Apr;228(4):1065–1074. [PubMed]
  • Nellans HN, Frizzell RA, Schultz SG. Brush-border processes and transepithelial Na and Cl transport by rabbit ileum. Am J Physiol. 1974 May;226(5):1131–1141. [PubMed]
  • Giannella RA, Drake KW. Effect of purified Escherichia coli heat-stable enterotoxin on intestinal cyclic nucleotide metabolism and fluid secretion. Infect Immun. 1979 Apr;24(1):19–23. [PMC free article] [PubMed]
  • Hughes JM, Murad F, Chang B, Guerrant RL. Role of cyclic GMP in the action of heat-stable enterotoxin of Escherichia coli. Nature. 1978 Feb 23;271(5647):755–756. [PubMed]
  • Taylor AE, Wright EM, Schultz SG, Curran PF. Effect of sugars on ion fluxes in intest-ine. Am J Physiol. 1968 Apr;214(4):836–842. [PubMed]
  • Smith PL, Field M. In vitro antisecretory effects of trifluoperazine and other neuroleptics in rabbit and human small intestine. Gastroenterology. 1980 Jun;78(6):1545–1553. [PubMed]
  • Dobbins J, Racusen L, Binder HJ. Effect of D-alanine methionine enkephalin amide on ion transport in rabbit ileum. J Clin Invest. 1980 Jul;66(1):19–28. [PMC free article] [PubMed]
  • Kachur JF, Miller RJ, Field M. Control of guinea pig intestinal electrolyte secretion by a delta-opiate receptor. Proc Natl Acad Sci U S A. 1980 May;77(5):2753–2756. [PMC free article] [PubMed]
  • van Rees H. Effects of ouabain and diphenylhydantoin on electrolyte and water shifts during intestinal absorption in the rat. Arch Int Pharmacodyn Ther. 1969 Dec;182(2):437–437. [PubMed]
  • Studer H, Kohler H, Bürgi H, Dorner E, Forster R, Rohner R. Goiters with high radioiodine uptake and other characteristics of iodine deficiency in rats chronically treated with aminoglutethimide. Endocrinology. 1970 Nov;87(5):905–914. [PubMed]
  • Rallison ML, Kumagai LF, Tyler FH. Goitrous hypothyroidism induced by amino-glutethimide, anticonvulsant drug. J Clin Endocrinol Metab. 1967 Feb;27(2):265–272. [PubMed]
  • Duckworth WC, Kitabchi AE. Stimulatory effect of aminoglutethimide on phenylethanolamine-N-methyl transferase (PNMT). Endocrinology. 1971 Feb;88(2):384–388. [PubMed]
  • Field M, McColl I. Ion transport in rabbit ileal mucosa. 3. Effects of catecholamines. Am J Physiol. 1973 Oct;225(4):852–857. [PubMed]
  • Horký K, Küchel O, Gregorvá I, Stárka L. Qualitative alterations in urinary 17-ketosteroid excretion during aminoglutethimide administration. J Clin Endocrinol Metab. 1969 Feb;29(2):297–299. [PubMed]
  • Santen RJ, Samojlik E, Lipton A, Harvey H, Ruby EB, Wells SA, Kendall J. Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer. Cancer. 1977 Jun;39(6 Suppl):2948–2958. [PubMed]
  • Taylor AA, Mitchell JR, Bartter FC, Snodgrass WR, McMurtry RJ, Gill JR, Jr, Franklin RB. Effect of aminoglutethimide on blood pressure and steroid secretion in patients with low renin essential hypertension. J Clin Invest. 1978 Jul;62(1):162–168. [PMC free article] [PubMed]
  • Rosoff L, Jr, Zia P, Reynolds T, Horton R. Studies of renin and aldosterone in cirrhotic patients with ascites. Gastroenterology. 1975 Sep;69(3):698–705. [PubMed]
  • Horký K, Küchel O. Aminoglutethimide (Elipten CIBA)--a new inhibitor of steroid biosynthesis. Ann Intern Med. 1969 Apr;70(4):866–867. [PubMed]
  • Mancheno-Rico E, Kuchel O, Nowaczynski W, Seth KK, Sasaki C, Dawson K, Genest J. A dissociated effect of amino-glutethimide on the mineralocorticoid secretion in man. Metabolism. 1973 Feb;22(2):123–132. [PubMed]
  • Binder HJ. Effect of dexamethasone on electrolyte transport in the large intestine of the rat. Gastroenterology. 1978 Aug;75(2):212–217. [PubMed]
  • Guandalini S, Kachur JF, Smith PL, Miller RJ, Field M. In vitro effects of somatostatin on ion transport in rabbit intestine. Am J Physiol. 1980 Feb;238(2):G67–G74. [PubMed]
  • Kimberg DV, Field M, Gershon E, Henderson A. Effects of prostaglandins and cholera enterotoxin on intestinal mucosal cyclic AMP accumulation. Evidence against an essential role for prostaglandins in the action of toxin. J Clin Invest. 1974 Mar;53(3):941–949. [PMC free article] [PubMed]
  • Schwartz CJ, Kimberg DV, Sheerin HE, Field M, Said SI. Vasoactive intestinal peptide stimulation of adenylate cyclase and active electrolyte secretion in intestinal mucosa. J Clin Invest. 1974 Sep;54(3):536–544. [PMC free article] [PubMed]
  • Bolton JE, Field M. Ca ionophore-stimulated ion secretion in rabbit ileal mucosa: relation to actions of cyclic 3',5'-AMP and carbamylcholine. J Membr Biol. 1977 Jun 30;35(2):159–173. [PubMed]
  • Charney AN, Donowitz M. Prevention and reversal of cholera enterotoxin-induced intestinal secretion by methylprednisolone induction of Na+-K+-ATPase. J Clin Invest. 1976 Jun;57(6):1590–1599. [PMC free article] [PubMed]
  • Batt RM, Peters TJ. Effects of prednisolone on the small intestinal mucosa of the rat. Clin Sci Mol Med. 1976 Jun;50(6):511–523. [PubMed]
  • Tutton PJ. Proliferation of epithelial cells in the jejunal crypts of adrenalectomized and adrenocortical hormone treated rats. Virchows Arch B Cell Pathol. 1973 Jul 22;13(3):227–232. [PubMed]
  • Feldman D, Funder JW, Edelman IS. Subcellular mechanisms in the action of adrenal steroids. Am J Med. 1972 Nov;53(5):545–560. [PubMed]
  • Kantrowitz F, Robinson DR, McGuire MB, Levine L. Corticosteroids inhibit prostaglandin production by rheumatiod synovia. Nature. 1975 Dec 25;258(5537):737–739. [PubMed]
  • Tashjian AH, Jr, Voelkel EF, McDonough J, Levine L. Hydrocortisone inhibits prostaglandin production by mouse fibrosarcoma cells. Nature. 1975 Dec 25;258(5537):739–741. [PubMed]
  • Matuchansky C, Mary JY, Bernier JJ. Further studies on prostaglandin E1-induced jejunal secretion of water and electrolytes in man, with special reference to the influence of ethacrynic acid, furosemide, and aspirin. Gastroenterology. 1976 Aug;71(2):274–281. [PubMed]
  • Pressley L, Funder JW. Glucocorticoid and mineralocorticoid receptors in gut mucosa. Endocrinology. 1975 Sep;97(3):588–596. [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...