Inhibitory effect of calcium channel blockers on .ALPHA.-adrenergic activation of glycogenolysis and calcium efflux in perfused rat liver.

Publisher Website
Google Scholar
Abstract
To verify the importance of Ca ions in mediating .alpha.-adrenergic stimulation, the effects of Ca channel blocker, verapamil, on phenylephrine-induced glycogenolysis and Ca efflux in perfused livers prepared from fed rats were determined. The blocker inhibited phenylephrine-induced glycogenolysis in a noncompetitive and dose-dependent manner between 50-500 .mu.M. It did not affect 2,4-dinitrophenol-induced glycogenolysis. It had no significant effect on 45Ca uptake by the perfused liver, but inhibited basal and phenylephrine-induxed efflux of 45Ca from 45Ca-loaded liver. The inhibitory effects on basal 45Ca release and phenylephrine-induced glycogenolysis and 45Ca release correlated very well. All effects of verapamil were reproduced by another Ca channel blocker, dilitiazem, suggesting that these effects are common to a variety of Ca channel blockers. The process of Ca influx and the function of phosphorylase per se apparently are not directly involved in the inhibitory action of the blocker. Verapamil may interfere with binding of the .alpha.-adrenergic agonist to the plasma membrane, but the good correlation between the inhibitory effects of verapamil on basal 45Ca release and on phenylephrine-induced release of 45Ca suggests another mechanism, involving Ca ions. The blocker appears to inhibit the glycogen phosphorylase activity induced by phenylephrine via a cell-membrane mechanism in which Ca ion flux changes are intimately involved.

This publication has 13 references indexed in Scilit: