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Inhibition of Na-K-Cl cotransport by amiloride analogues is associated with stimulation of cyclic AMP-dependent protein kinase

RD Feldman and SJ Dixon

Department of Medicine, University of Western Ontario, London, Canada.

Analogues of amiloride are widely used as pharmacological probes for inhibition of sodium-hydrogen counter-transport. In Jurkat cells, a leukemic T lymphocyte cell line, analogues of amiloride are also potent inhibitors 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 kinase activity. The present studies indicate that beta-adrenoceptor agonists and analogues of amiloride both act to inhibit Na-K-Cl cotransport and both stimulate cAMP-dependent protein kinase activity. Furthermore, these studies demonstrate a novel mechanism by which amiloride analogues may mediate effects separately from inhibition of sodium- hydrogen exchange.

Volume 44, Issue 2, pp. 393-398, 08/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics




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