INHIBITION OF NA-K-CL COTRANSPORT BY AMILORIDE ANALOGS IS ASSOCIATED WITH STIMULATION OF CYCLIC-AMP-DEPENDENT PROTEIN-KINASE

Analogues of amiloride are widely used as pharmacalogical probes for i nhibition of sodium-hydrogen counter-transport. In Jurkat cells, a leu kemic T lymphocyte cell line, analogues of amiloride are also potent i nhibitors of Na-K-Cl cotransport. The effects of these agents are not additive with those of beta-adrenoceptor agonists (which inhibit Na-K- Cl cotransport presumably by stimulation of adenylyl cyclase). Further , analogues of amiloride potently stimulate cAMP-dependent protein kin ase activity. The present studies indicate that beta-adrenoceptor agon ists and analogues of amiloride both act to inhibit Na-K-Cl cotranspor t and both stimulate cAMP-dependent protein kinase activity. Furthermo re, these studies demonstrate a novel mechanism by which amiloride ana logues may mediate effects separately from inhibition of sodium-hydrog en exchange.