Catecholamines inhibit insulin release independently of changes in cytosolic free Ca2+

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Abstract
Effects of catecholamines on insulin release were studied using isolated rat pancreatic islets permeabilized with digitonin whose cytosolic Ca2+ concentration ([Ca2+]i) was clamped with Ca-EGTA buffer. Adrenaline or noradrenaline dose-dependently inhibited insulin release induced by raising Ca2+ concentrations. The inhibitory effect of adrenaline was antagonized by yohimbine, an .alpha.2-adrenergic blocker, but not by prazosin, an .alpha.1-adrenergic blocker. Adrenaline also inhibited insulin release stimulated by increasing cyclic AMP or by activating protein kinase C in Ca2+-clamped islets. The findings suggest that catecholamines, via .alpha.2-adrenergic receptors, inhibit insulin release by acting on a step independent of and probably distal to changes in [Ca2+]i in stimulus-secretion coupling.