Interaction between Ca2+, verapamil, and ketanserin in rat tail artery and aorta

To elucidate the complex pharmacological actions of the 5-hydroxytryptamine2A (5-HT2A)-receptor antagonist ketanserin, we investigated certain similarities between these properties and those of the Ca antagonist verapamil. We investigated the interactions of Ca2+, ketanserin, and verapamil on the contractile responses to 5-HT in rat isolated perfused tail artery and aortic strip preparations. In both tissues, variations in perfusate [Ca2+] had similar effects: threshold contractile concentrations of 5-HT were unaffected, and the upper ends of the 5-HT dose-response curves were augmented or decreased by increased or decreased [Ca2+], respectively. Ketanserin competitively antagonised contractile responses to 5-HT in both tissues, with mean pA2 values of 9.17 and 7.46 in tail artery and aorta, respectively. However, increase in [Ca2+], with addition of ketanserin, caused a parallel leftward shift of the 5-HT dose-response curve in tail arteries with a nonparallel leftward shift in aorta. Verapamil nonsurmountably antagonised contractile responses to 5-HT in aorta and competitively antagonised 5-HT in tail arteries. Subsequent addition of ketanserin to the verapamil-containing perfusate caused a further shift to the right of the 5-HT dose-response curve in aorta, but had no additional antagonist effect above that of verapamil alone on tail artery responses to 5-HT. The results show that although the pharmacological properties of ketanserin and verapamil overlapped, there were marked differences between the pharmacologies of the 5-HT2A-receptors in the two tissues studied, suggesting either that the mechanism of the 5-HT-induced influx of Ca2+ is different in the two tissues or that the 5-HT2A receptors differ structurally between tissues.