Glucocorticoids inhibit colonic aldosterone-induced conductive Na+ absorption in adrenalectomized rat.
Low-dose glucocorticoids induce only electroneutral Na absorption in rat colon. High-dose dexamethasone induces both electroneutral and electrogenic Na absorption. Aldosterone induces only electrogenic Na absorption and inhibits basal electroneutral transport in distal colon. To define the interrelationship between glucocorticoid-mediated and aldosterone-mediated Na absorption, adrenalectomized rats were treated with aldosterone and either glucocorticoid-receptor-specific doses of dexamethasone or the specific glucocorticoid RU26988. In combination the steroids did not increase Na and Cl absorption in proximal and distal colon and transmural potential difference (PD) and K secretion in distal colon as much as aldosterone alone. Na absorption was not inhibited by spironolactone or amiloride (10(-4) M). Transport in both segments was by Na-H exchange as demonstrated by marked inhibition by amiloride (10(-3) M) and the Na-H antiport inhibitor 5-(N-ethyl-N-isopropyl)amiloride. Thus glucocorticoids not only decreased Na absorption but also produced a marked qualitative change in the mode of Na absorption in aldosterone-treated rats. Acute dexamethasone infusion in rats pretreated with aldosterone decreased Na absorption and transmural PD within 30 min, suggesting inhibition of electrogenic Na absorption at a step distal to synthesis of aldosterone-induced proteins. These findings suggest that upregulation of one Na absorptive mechanism downregulates the other. This may explain why in intact unstressed rats there is little or no conductive Na absorption, despite sufficient endogenous steroid to occupy the aldosterone receptor. It may also explain why in proximal colon of intact rats, despite the presence of aldosterone receptors, even prolonged aldosterone exposure does not induce significant conductive Na absorption.
Bastl
C P
CP
Department of Medicine, Temple University Health Sciences Center, Philadelphia, Pennsylvania 19140.
Schulman
G
G
Cragoe
E J
EJ
D000042:Absorption; D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers; D013148:Spironolactone / Q000494:pharmacology
D000732:Androstanols; D002352:Carrier Proteins; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; D013148:Spironolactone; D000450:Aldosterone; C038341:RU 26988; D003907:Dexamethasone; D012964:Sodium