Agonistic and antagonistic effects of various α-adrenergic agonists in human platelets

Summary

In human platelets, the effects of various α-adrenergic agonists were studied on platelet aggregation and adenylate cyclase activity. Out of many phenylethylamine derivatives tested, only some catecholamines were able to act as α-adrenergic agonists inducing platelet aggregation and inhibition of adenylate cyclase with the order of potency: adrenaline > noradrenaline>α-methylnoradrenaline. Other phenylethylamine and imidazoline derivatives, which act as potent α-adrenergic agonists in various systems, neither induced primary aggregation nor adenylate cyclase inhibition, when tested at concentrations up to 1 mM. Since binding studies indicated high affinities of these agents to the platelet α-adrenergic receptor, their effects on adrenaline-induced aggregation and adenylate cyclase inhibition were studied.

Both types of α-adrenergic agonists tested, phenylethylamine and imidazoline derivatives, prevented adrenaline-induced aggregation and adenylate cyclase inhibition. The imidazolines, xylometazoline, oxymetazoline, naphazoline, clonidine and tetryzolin, were the most effective antagonists with similar potencies as observed with the typical α-adrenergic antagonists, phentolamine and yohimbine. Phenylethylamine derivatives such as phenylephrine, methoxamine, synephrine and norfenefrine, similarly antagonized the adrenaline-induced responses but higher concentrations were required. The potencies of these phenylethylamine derivatives were similar to those of the classical α-adrenergic antagonists, phenoxybenzamine and azapetine. The results indicate that the platelet α-adrenergic receptor, which has many similarities with the α₂-adrenergic receptor with regard to affinities of various α-adrenergic agonists, completely differs from that found in other tissues, inasmuch as only some catecholamines acted as agonists whereas other phenylethylamine derivatives and imidazoline derivatives acted as antagonists.