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

• Published in: Acta physiologica Scandinavica 1988-07, Vol.133 (3), p.407-416
• Main Authors: VINGE, E., ANDERSSON, T. L. G., LARSSON, B.
• Format: Article
• Language: English
• Subjects: 5-HT-receptors; Adrenergic alpha-Antagonists - pharmacology; aggregation; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; calcium antagonists; Calcium Channel Blockers - pharmacology; cell aggregation; Diltiazem - pharmacology; Epinephrine - pharmacology; human platelets; Humans; Ketanserin - pharmacology; man; Medical sciences; Nifedipine - pharmacology; Pharmacology. Drug treatments; Phentolamine - pharmacology; Platelet Aggregation - drug effects; platelets; Radioligand Assay; radioligand binding; Serotonin - pharmacology; Verapamil - pharmacology; Yohimbine - pharmacology; α-adrenoceptors
• ISSN: 0001-6772; 1365-201X
• 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 α‐adrenoceptor‐antagonists phentolamine (α1 and α2) and rauwolscine (α2), and the s‐HT2‐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‐α‐ergocryptine and [3H]rauwolscine on human platelet membranes showed equal numbers of binding sites, suggesting that only α2‐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 α‐adrenoceptor antagonistic properties but also exerts 5‐HT‐receptor blocking effects. This was not found with the other calcium channel blockers examined (nifedipine, diltiazem).