Okoro E O
Department of Clinical Pharmacology, Royal Northshore Hospital, St Leonards, NSW, Australia.
J Pharm Pharmacol. 1999 Aug;51(8):953-7. doi: 10.1211/0022357991773221.
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 x 10(-11), 6.6 x 10(-11), 1.5 x 10(-9), 1.7 x 10(-9), 3.2 x 10(-7), 5.4 x 10(-7), 9.7 x 10(-10), 1.9 x 10(-8), 5.0 x 10(-7) and 6.4 x 10(-7), respectively. The same compounds antagonized K+-induced rat aortic contractions with the rank order of potency (mean IC50, M): felodipine (7.0 x 10(-11)) > nifedipine (4.8 x 10(-9)) > sodium nitroprusside (4.1 x 10(-8)) > verapamil (5.5 x 10(-8)) > cyproheptadine (6.2 x 10(-8)) > diltiazem (4.1 x 10(-7)) > cinnarizine (1.3 x 10(-6)) > ritanserin (1.8 x 10(-6)) > ketanserin (9.0 x 10(-6)) > mianserin (2.0 x 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.
我们之前已经表明，去除缓冲液中的Ca2+可显著降低5-羟色胺（5-HT）诱导的最大收缩。我们现在研究了L型钙通道阻滞剂和5-HT2受体拮抗剂对大鼠主动脉中5-HT和K+诱导的收缩的影响，以探讨L型钙通道阻断与5-HT2受体拮抗之间存在关联的可能性。硝普钠、非洛地平、硝苯地平、地尔硫卓、桂利嗪、维拉帕米、利坦色林、赛庚啶、酮色林和米安色林抑制大鼠主动脉5-HT诱导的收缩，平均半数抑制浓度（IC50值，即导致50%抑制的浓度，单位为摩尔）分别为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)和6.4×10(-7)。相同的化合物拮抗K+诱导的大鼠主动脉收缩，其效价顺序（平均IC50，单位为摩尔）为：非洛地平（7.0×10(-11)）>硝苯地平（4.8×10(-9)）>硝普钠（4.1×10(-8)）>维拉帕米（5.5×10(-8)）>赛庚啶（6.2×10(-8)）>地尔硫卓（4.1×10(-7)）>桂利嗪（1.3×10(-6)）>利坦色林（1.8×10(-6)）>酮色林（9.0×10(-6)）>米安色林（2.0×10(-5)）。这些数据表明，对5-HT诱导收缩的效价与对K+去极化收缩反应的效价之间存在高度显著的相关性（r = 0.81，P = 0.03），并提示L型钙通道阻滞剂和5-HT2受体拮抗剂在大鼠主动脉中的药理学存在重叠。
