title: Effects of some calcium antagonists on aggregation by adrenalin and serotonin and on alpha-adrenoceptor radioligand binding in human platelets.
abstract: 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).
authors.affiliation: Department of Clinical Pharmacology, University Hospital, Lund, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Vinge
authors.forename: T L
authors.initials: TL
authors.lastname: Andersson
authors.forename: B
authors.initials: B
authors.lastname: Larsson
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D007650:Ketanserin / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011869:Radioligand Assay; D012701:Serotonin / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D015016:Yohimbine; D012701:Serotonin; D007650:Ketanserin; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D004837:Epinephrine; D010646:Phentolamine