THE ALPHA(2)-ADRENERGIC RECEPTOR IS MORE EFFECTIVE THAN THE GALANIN RECEPTOR IN ACTIVATING G-PROTEINS IN RINM5F BETA-CELL MEMBRANES

Activated receptors for galanin and norepinephrine, and for several ot her agonists, inhibit insulin release from pancreatic beta-cells via p ertussis toxin-sensitive G(i)- and G(o)-proteins and by acting on at l east four cellular mechanisms. These mechanisms include repolarization via activation of the ATP-sensitive potassium (K-ATP) channel, inhibi tion of adenylyl cyclase, and inhibition by unknown mechanism at a ''d istal'' site. For norepinephrine and galanin there is also inhibition of the L-type Ca2+ channel. Consequently, during simultaneous activati on by multiple agonists, the effectiveness with which a receptor inter acts with the G-proteins will, to some extent, determine the responses . This could have important consequences for the beta-cell. Therefore, the G protein interactions of two activated receptors, those for nore pinephrine and galanin, were compared in the same beta-cell membranes. Measurements were made of the rates of receptor-G-protein interaction (by GTP gamma S binding) and of the rates of turnover of G-proteins ( by GTPase activity). A comparison was also made of the ability of nore pinephrine and galanin to facilitate ADP ribosylation of the alpha-sub units of G(i) and G(o) by cholera toxin (CTX). Such CTX-induced ADP ri bosylation of G(i) and G(o) occurs during G-protein interaction with a n activated receptor. By measurement of the number of receptors in the membrane preparation used, the relative effectiveness of the two rece ptors was assessed. The alpha(2)-adrenergic receptor was found to be m arkedly more effective than the galanin receptor in activating G-prote ins.