Biphasic effect of the alpha-adrenolytic phentolamine on hormone-stimulated formation of cyclic adenosine-3',5'-monophosphate in isolated fat cells of rats.

Isolated fat cells from rat epididymal adipose tissue were incubated with various lipolytic hormones in the absence and presence of the alpha-adrenergic blocking agent phentolamine. Lipolysis, stimulated by noradrenaline, isoproterenol, or ACTH, was inhibited dose-dependently by phentolamine. At concentrations of phentolamine where lipolysis was already inhibited, phentolamine had a biphasic effect on hormone-stimulated formation of cAMP. Low concentrations of phentolamine enhanced cAMP formation, while high concentrations inhibited cAMP. The additional increase of cAMP formation by phentolamine was only seen with maximally effective concentrations of noradrenaline, isoproterenol, and ACTH. Half-maximally effective concentrations were invariably inhibited by phentolamine. The activity of noradrenaline-stimulated adenylate cyclase of fat-cell plasma membranes was inhibited by phentolamine, whereas cAMP phosphodiesterase activity was unaffected.