Low-dose glucocorticoids stimulate electroneutral NaCl absorption in rat colon.
Glucocorticoids, not aldosterone, may regulate basal colonic NaCl transport. Aldosterone induces spironolactone-inhibitable, amiloride-inhibitable conductive Na absorption but basal transport is electroneutral and amiloride and spironolactone resistant. We examined in vivo the Na absorptive pathway induced by glucocorticoid receptor specific doses of glucocorticoid using various amiloride analogues. Doses of dexamethasone sufficient to co-occupy aldosterone receptors produced amiloride-sensitive Na absorption in proximal and distal colon. Low doses of dexamethasone or the specific glucocorticoid RU26988 markedly stimulated Na absorption but did so by an amiloride-resistant mechanism. The Na-H antiport inhibitor, 5-N-ethyl-N-isopropylamiloride (NENIA) eliminated glucocorticoid-induced Na and Cl absorption without changing transmural potential difference (PD) in proximal and distal colon (Ki = 0.7 x 10(-7) M). NENIA had no effect on aldosterone-induced transport. NENIA (10(-5) M) almost eliminated Na absorption in adrenal intact animals if infused early in the experimental protocol. With time, NENIA resistance developed, corresponding with the previously documented rise in endogenous aldosterone. Thus glucocorticoids induce an electroneutral Na absorptive pathway that may be the luminal Na-H antiport, suggesting that glucocorticoids regulate adrenal-dependent electroneutral Na absorption in rat colon.
Bastl
C P
CP
Department of Medicine, Temple University Health Sciences Center, Philadelphia, Pennsylvania 19140.
Schulman
G
G
Cragoe
E J
EJ
D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000378:metabolism*
D000732:Androstanols; D002712:Chlorides; C013407:benzamil; D012965:Sodium Chloride; D000450:Aldosterone; C038341:RU 26988; D000584:Amiloride; D003907:Dexamethasone; D012964:Sodium; C039614:ethylisopropylamiloride