Effects of spironolactone and amiloride on corticosteroid-induced changes in colonic function

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Abstract
Mineralocorticoid and glucocorticoid effects on colonic electrolyte absorption were compared by examining the alterations caused by spironolactone and amiloride in corticosteroid-treated rats. Animals were treated for 3 days with deoxycorticosterone acetate (DOCA; 0.5 mg .cntdot. 100 g-1 .cntdot. day-1), methylprednisolone (MP; 3 or 0.5 mg .cntdot. 100 g-1 .cntdot. day-1) and spironolactone (14 mg .cntdot. 100 g-1 .cntdot. day-1 i.m.) singly or in combination. On day 4, rats were anesthetized with pentobarbital sodium and perfused in vivo with Ringer-HCO3 solution. Both doses of MP and DOCA increased net colonic Na and water absorption and mucosal Na-K-ATPase activity. Concurrent spironolactone treatment completely prevented these effects in DOCA-treated rats but had no effect in MP-treated rats. Untreated, MP-treated, and DOCA-treated animals were perfused with a Ringer-HCO3 solution containing 1 mM amiloride. Amiloride reduced net colonic Na and water absorption, transmural potential difference, and K secretion in all rats by approximately 55%. These effects were almost immediate and completely reversible. Evidently, different receptors mediate the colonic effects of mineralocorticoids and glucocorticoids. These corticosteroids may not differ in their relative effects on amiloride-sensitive and amiloride-resistant colonic Na transport processes.

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