Effects of some calcium antagonists on aggregation by adrenalin and serotonin and on alpha-adrenoceptor radioligand binding in human platelets.
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).
Vinge
E
E
Department of Clinical Pharmacology, University Hospital, Lund, Sweden.
Andersson
T L
TL
Larsson
B
B
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
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D015016:Yohimbine; D012701:Serotonin; D007650:Ketanserin; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D004837:Epinephrine; D010646:Phentolamine