Activated receptors for galanin and norepinephrine, and for several other agonists, inhibit insulin release from pancreatic β-cells via pertussis toxin–sensitive Gi- and Go-proteins and by acting on at least four cellular mechanisms. These mechanisms include repolarization via activation of the ATP-sensitive potassium (KATP) channel, inhibition of adenylyl cyclase, and inhibition by unknown mechanism at a “distal” site. For norepinephrine and galanin there is also inhibition of the L-type Ca2+ channel. Consequently, during simultaneous activation by multiple agonists, the effectiveness with which a receptor interacts with the G-proteins will, to some extent, determine the responses. This could have important consequences for the β-cell. Therefore, the G-protein interactions of two activated receptors, those for norepinephrine and galanin, were compared in the same β-cell membranes. Measurements were made of the rates of receptor–G-protein interaction (by GTPγS binding) and of the rates of turnover of G-proteins (by GTPase activity). A comparison was also made of the ability of norepinephrine and galanin to facilitate ADP ribosylation of the α-subunits of Gi and Go by cholera toxin (CTX). Such CTX-induced ADP ribosylation of Gi and Go occurs during G-protein interaction with an activated receptor. By measurement of the number of receptors in the membrane preparation used, the relative effectiveness of the two receptors was assessed. The α2adrenergic receptor was found to be markedly more effective than the galanin receptor in activating G-proteins.

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