title: Effects of corticosteroid hormones on the electrophysiology of rat distal colon: implications for Na+ and K+ transport.
abstract: 1. Conventional microelectrodes, the Na+ channel blocker amiloride (0.1 mM), and the K+ channel blocker tetraethylammonium chloride (TEA, 30 mM) were used to examine the effects of corticosteroid hormones administered in vivo on the Na+ and K+ transport properties of isolated rat distal colon. The cell membrane changes induced by aldosterone (a specific mineralocorticoid), RU 28362 (a synthetic glucocorticoid with negligible affinity for mineralocorticoid receptors), and dexamethasone (an activator of both mineralocorticoid and glucocorticoid receptors) were compared. 2. In control animals, there was no amiloride-sensitive apical Na+ conductance, and only a relatively small TEA-sensitive apical K+ conductance. 3. Hyperaldosteronism secondary to dietary Na+ depletion for 10-14 days, dexamethasone (600 micrograms 100 g-1 day-1 for 3 days), and RU 28362 (600 micrograms 100 g-1 day-1 for 3 days) induced amiloride-sensitive electrogenic Na+ transport, with the potency of aldosterone greater than dexamethasone greater than RU 28362. 4. With each corticosteroid, increased electrogenic Na+ transport reflected enhanced apical Na+ conductance, and in the case of aldosterone and dexamethasone, 3.3-fold and 2-fold increases respectively in the maximum activity of the basolateral Na+-K+ pump. In contrast, RU 28362 suppressed the maximum activity of the basolateral Na+-K+ pump by 45%. 5. All three corticosteroids enhanced the K+ conductance of the apical membrane, with the potency of aldosterone greater than dexamethasone greater than RU 28362. 6. Co-administration of spironolactone (5 mg 100 g-1 day-1) inhibited the effects of aldosterone on Na+ and K+ transport, but in dexamethasone-treated animals spironolactone resulted in a pattern of response similar to that found in RU 28362-treated animals. 7. The results support the view that mineralocorticoid receptors mediate changes in colonic Na+ and K+ transport which differ quantitatively and qualitatively from those mediated by glucocorticoid receptors. Dexamethasone and similar 'glucocorticoids' activate both types of receptor, with an overall epithelial response which mimics that induced by aldosterone.
authors: Department of Medicine, Hope Hospital (University of Manchester School of Medicine), Salford.
authors: H J
authors: HJ
authors: Binder
authors: F
authors: F
authors: McGlone
authors: G I
authors: GI
authors: Sandle
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology; D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000493:pharmacokinetics*; D013148:Spironolactone / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D000732:Androstanols; D013757:Tetraethylammonium Compounds; D013148:Spironolactone; D000450:Aldosterone; D019789:Tetraethylammonium; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D000584:Amiloride; D003907:Dexamethasone; D012964:Sodium; D011188:Potassium