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

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 . 100 g-1 . day-1), methylprednisolone (MP; 3 or 0.5 mg . 100 g-1 . day), and spironolactone (14 mg . 100 g-1 . day-1 im) 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 sodium 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 sodium and water absorption, transmural potential difference, and potassium secretion in all rats by approximately 55%. These effects were almost immediate and completely reversible. These findings in the rat suggest that 1) different receptors mediate the colonic effects of mineralocorticoids and glucocorticoids and 2) these corticosteroids do not differ in their relative effects on amiloride-sensitive and amiloride-resistant colonic sodium transport processes.