Okoro E O, Marwood J F, Stokes G S
Clinical Pharmacology Department, Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
J Cardiovasc Pharmacol. 1995 Apr;25(4):603-10. doi: 10.1097/00005344-199504000-00014.
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.
为阐明5-羟色胺2A（5-HT2A）受体拮抗剂酮色林复杂的药理作用，我们研究了这些特性与钙拮抗剂维拉帕米特性之间的某些相似性。我们研究了钙离子、酮色林和维拉帕米对大鼠离体灌注尾动脉和主动脉条制备物中5-羟色胺收缩反应的相互作用。在这两种组织中，灌注液中[Ca2+]的变化具有相似的作用：5-羟色胺的阈收缩浓度不受影响，5-羟色胺剂量-反应曲线的上限分别因[Ca2+]的增加或减少而升高或降低。酮色林在两种组织中均竞争性拮抗5-羟色胺的收缩反应，在尾动脉和主动脉中的平均pA2值分别为9.17和7.46。然而，在加入酮色林的情况下，[Ca2+]的增加导致尾动脉中5-羟色胺剂量-反应曲线平行左移，而在主动脉中则为非平行左移。维拉帕米不可逾越地拮抗主动脉中5-羟色胺的收缩反应，并竞争性拮抗尾动脉中的5-羟色胺。随后在含维拉帕米的灌注液中加入酮色林，导致主动脉中5-羟色胺剂量-反应曲线进一步右移，但对尾动脉对5-羟色胺的反应没有单独维拉帕米之外的额外拮抗作用。结果表明，尽管酮色林和维拉帕米的药理特性有重叠，但在所研究的两种组织中，5-HT2A受体的药理学存在显著差异，这表明要么5-羟色胺诱导的Ca2+内流机制在两种组织中不同，要么5-HT2A受体在组织间结构不同。
