Paper| Volume 40, ISSUE 6, P757-767, December 15, 1985

Characterization of human platelet beta-adrenoceptors

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      The widespread use of beta-adrenoceptor antagonists againist hypertension, angina pectoris and migraine or as a preventive treatment after myocardial infarction has encouraged us to investigate the effects of these drugs on platelet function. The aim of this study was to examine whether beta-blocking drugs interfere with platelet beta- adrenoceptors and whether this dependency is related to their selectivity for beta-adrenoceptor subtypes. Beta-adrenoceptor stimulation of human platelets with isoprenaline increased cyclic AMP (cAMP), which is known to inhibit platelet aggregation. Furthermore, our studies showed that cAMP formation Math Eq was stimulated by non-selective and beta2-selective agonists, but not by the predominant beta-agonist prenalterol. Isoprenaline- stimulated cAMP formation was blocked by the non- selective beta-adrenoceptor antagonists propranolol, timolol, and alprenolol, while the betal-selective antagonists atenolol and metoprolol had no influence on an isoprenaline-induced cAMP formation. Receptor binding studies using (3H-dyhydroalprenolol revealed an IC50 value for propranolol of 85 nM, while metoprolol only displaced the bound (33H)-dihydroalprenolol at far higher concentrations (IC50, 20 μM). We conclude that the human platelet beta-adrenoceptors are mainly of the beta2 - subtype and that beta-adrenoceptor antagonists, especially the non-selective antagonists interfere with platelet function assessed as platelet cAMP formation.


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