Overlap in the Pharmacology of L-type Ca2+-channel Blockers and 5-HT2 Receptor Antagonists in Rat Aorta

Abstract

Abstract We have previously shown that elimination of buffer Ca2+ markedly reduced maximum 5-HT-induced contractions. We have now investigated the effect of L-type Ca2+-channel blockers and 5-HT2 receptor antagonists on 5-HT- and K+-induced contractions in rat aorta to explore the possibility of a relationship between blockade of L-type Ca2+ channels and 5-HT2 receptor antagonism. Sodium nitroprusside, felodipine, nifedipine, diltiazem, cinnarizine, verapamil, ritanserin, cyproheptadine, ketanserin and mianserin inhibited 5-HT-induced contractions of rat aorta with mean IC50 values (concentration (M) resulting in 50% inhibition) of 2.2 × 10−11, 6.6 × 10−11, 1.5 × 10−9,1.7 × 10−9, 3.2 × 10−7, 5.4 × 10−7, 9.7 × 10−10, 1.9 × 10−8, 5.0 × 10−7 and 6.4 × 10−7, respectively. The same compounds antagonized K+-induced rat aortic contractions with the rank order of potency (mean IC50, M): felodipine (7.0 × 10−11) > nifedipine (4.8 × 10−9) > sodium nitroprusside (4.1 × 10−8) > verapamil (5.5 × 10−8) > cyproheptadine (6.2 × 10-8) > diltiazem (4.1 × 10−7) > cinnarizine (1.3 × 10−6) > ritansarin(1.8 × 10−6) > ketanserin (9.0 × 10−6) > mianserin (2.0 × 10−5). These data are indicative of a highly significant correlation (r = 0.81, P = 0.03) between potency against 5-HT-induced contraction and that against contractile response to K+ depolarization, and suggest overlap of the pharmacology of L-type Ca2+-channel blockers and 5-HT2 receptor antagonists in rat aorta.