Characterization of alpha- and beta-adrenergic receptors linked to human platelet adenylate cyclase.

Abstract

Adrenaline and noradrenaline cause aggregation of human platelets through α-adrenergic receptors, whereas isoprenaline through β-adrenergic receptors can inhibit aggregation. Either type of adrenergic receptors is coupled to platelet adenylate cyclase. Stimulation and inhibition of adenylate cyclase by β-and α-adrenergic stimulants, respectively, had been demonstrated in human platelet lysates. These effects were characterized with regard to the effectiveness of various agonists and antagonists. Reduction of platelet adenylate cyclase activity was observed only with L-adrenaline and L-noradrenaline. This inhibitory effect, which was increased in the presence of a β-adrenergic blocking agent, was half-maximal at about 1 to 2×10−6 M adrenaline, and maximal inhibition (by 50–60%) was observed at about 3×10−5M. Various other catecholamine and imidazoline derivatives that act as α-adrenergic agonists in other cell types neither induced aggregation nor affected the enzyme activity. Adrenaline-induced inhibition of platelet adenylate cyclase was prevented by α-adrenergic blocking agents. These compounds inhibited the effects of adrenaline on aggregation and on adenylate cyclase with similar efficacies. Dihydrogenated ergot alkaloids were more effective than phentolamine and yohimbine; phenoxybenzamine, tolazoline and azapetine were least effective. Adrenaline-induced inhibition of platelet adenylate cyclase was reversed by phentolamine without apparent lag phase. In the presence of α-adrenergic blocking agents, adrenaline was capable of increasing adenylate cyclase activity between 20 and 50%. Only adrenaline and isoprenaline stimulated adenylate cyclase activity; other compounds that stimulate β-adrenergic receptors in other cell types, including β-adrenergic stimulants, had no effect on the activity of the platelet enzyme. The stimulatory effect of adrenaline was prevented by various β-adrenergic blocking agents including pindolol and propranolol. Preferentially β-adrenergic receptor blocking agents such as practolol and atenolol were without effect. These findings indicate that the spectrum of compounds capable of exhibiting intrinsic activity through α- and β-adrenergic receptors of human platelets is very narrow and that either type of platelet adrenergic receptors appears to differ from those found in other cell types.