The present study was undertaken to determine whether activation of the Na+/H+ antiport regulates the bradykinin (BK)-induced Ca++ transient in Madin-Darby canine kidney cells. An amiloride analog, 5-N-N-ethyl[2-methoxy 5-nitrobenzyl]amiloride (L651,548), led to a dose-dependent inhibition of the BK-induced Ca++ transient (K(i) = 9 μM), and this effect was eliminated in high external Na+. Zero external Na+ failed to inhibit the BK-induced Ca++ release, suggesting L651,548 is not acting through inhibition of the Na+/H+ antiport. Use of monovalent ionophores to adjust the intracellular pH demonstrated changes in peak Ca++ release by BK only over wide pH ranges. Furthermore, studies revealed L651,548 was much more potent at inhibiting pH recovery (K(i) = 55 nM) than BK-induced Ca++ release. Studies in saponin-permeabilized cells demonstrated no effect of L651,548 on inositol trisphosphate-induced Ca++ release. Whole cell [3H] BK binding studies indicated a dose-dependent inhibition by L651,548. We conclude that the Na+/H+ antiport does not play a critical role in control of BK-induced Ca++ release in Madin-Darby canine kidney cells. Also, the amiloride analog L651,548 reduces BK Ca++ release by inhibition of BK receptor binding in Madin-Darby canine kidney cells.
|Number of pages||5|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 1989|