Effects of some calcium antagonists on aggregation by adrenalin and serotonin and on alpha-adrenoceptor radioligand binding in human platelets

• Published in: Acta physiologica Scandinavica Vol. 133; no. 3; p. 407
• Main Authors: Vinge, E, Andersson, T L, Larsson, B
• Format: Journal Article
• Language: English
• Published: England 01.07.1988
• Subjects: Adrenergic alpha-Antagonists - pharmacology; Calcium Channel Blockers - pharmacology; Diltiazem - pharmacology; Epinephrine - pharmacology; Humans; Ketanserin - pharmacology; Nifedipine - pharmacology; Phentolamine - pharmacology; Platelet Aggregation - drug effects; Radioligand Assay; Serotonin - pharmacology; Verapamil - pharmacology; Yohimbine - pharmacology
• ISSN: 0001-6772
• DOI: 10.1111/j.1748-1716.1988.tb08423.x

The inhibitory effects of verapamil, nifedipine and diltiazem, representatives of different classes of calcium antagonists, were studied on aggregation of human platelets induced by adrenalin and serotonin (5-HT). For references, the alpha-adrenoceptor-antagonists phentolamine (alpha 1 and alpha 2) and rauwolscine (alpha 2), and the 5-HT 2-receptor-antagonist ketanserin were included. Verapamil in the concentration range 10(-6) 10(-4) M inhibited both adrenalin- and serotonin-induced aggregation in a concentration-dependent manner, whereas nifedipine and diltiazem had little or no effect. Phentolamine and rauwolscine were clearly weaker than verapamil as antagonists of serotonin, and ketanserin lacked effect on adrenalin-induced aggregation. Binding studies with [3H]dihydro-alpha-ergocryptine and [3H]rauwolscine on human platelet membranes showed equal numbers of binding sites, suggesting that only alpha 2-adrenoceptors were present. In the same concentration range as inhibition of aggregation was obtained, verapamil inhibited binding of either radioligand. Nifedipine, diltiazem and 5-HT were all poor inhibitors of radioligand binding. The results suggest that verapamil at high concentrations not only has alpha-adrenoceptor antagonistic properties but also exerts 5-HT-receptor blocking effects. This was not found with the other calcium channel blockers examined (nifedipine, diltiazem).