Cohen M L, Carpenter R, Schenck K, Wittenauer L, Mason N
J Pharmacol Exp Ther. 1986 Sep;238(3):860-7.
The present study explored the calcium source used in serotonin (5-HT)-induced contractions mediated by 5-HT2 receptor activation in the rat uterus and jugular vein in vitro. In the rat uterus, the calcium channel antagonists, nitrendipine and diltiazem, and the neuroleptic agents, trifluoperazine (TFP) and pimozide, antagonized potently and noncompetitively 5-HT-induced contractions. These data are compatible with the contention that 5-HT-induced contractions in uterine smooth muscle require extracellular sources of calcium. In contrast, neither diltiazem nor nitrendipine inhibited the contractile response to 5-HT in the rat jugular vein although 5-HT-induced contractions in the jugular vein required the presence of extracellular calcium. This difference in sensitivity to calcium channel antagonists between the uterus and jugular vein was not related to differences in the receptor occupancy-response curves for 5-HT as these were similar in the rat uterus and jugular vein. Furthermore, in the jugular vein, neither diltiazem nor nitrendipine were markedly effective in blocking contractions produced by potassium chloride, an agent that activates voltage-dependent calcium channels, suggesting that this tissue lacks calcium channels susceptible to blockade by conventional calcium channel antagonists. Although responses to 5-HT in the jugular vein were only affected marginally by calcium channel antagonists, TFP and pimozide produced concentration-dependent rightward parallel shifts of 5-HT-induced contractions in the jugular vein. Furthermore, both TFP and pimozide showed high affinity at 5-HT2 binding sites in rat brain cortical membranes and the apparent dissociation constant at 5-HT2 receptors in the jugular vein was 38 and 31 nM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究探讨了在体外大鼠子宫和颈静脉中，5-羟色胺（5-HT）通过激活5-HT2受体介导收缩时所使用的钙源。在大鼠子宫中，钙通道拮抗剂尼群地平和地尔硫䓬，以及抗精神病药物三氟拉嗪（TFP）和匹莫齐特，能有效且非竞争性地拮抗5-HT诱导的收缩。这些数据支持以下观点：5-HT诱导子宫平滑肌收缩需要细胞外钙源。相比之下，地尔硫䓬和尼群地平均未抑制大鼠颈静脉对5-HT的收缩反应，尽管5-HT诱导颈静脉收缩需要细胞外钙的存在。子宫和颈静脉对钙通道拮抗剂敏感性的这种差异与5-HT的受体占据-反应曲线差异无关，因为它们在大鼠子宫和颈静脉中相似。此外，在颈静脉中，地尔硫䓬和尼群地平对氯化钾（一种激活电压依赖性钙通道的药物）引起的收缩均无明显的阻断作用，这表明该组织缺乏易被传统钙通道拮抗剂阻断的钙通道。尽管颈静脉对5-HT的反应仅受到钙通道拮抗剂的轻微影响，但TFP和匹莫齐特使颈静脉中5-HT诱导的收缩产生浓度依赖性的向右平行位移。此外，TFP和匹莫齐特在大鼠脑皮质膜的5-HT2结合位点均显示出高亲和力，颈静脉中5-HT2受体的表观解离常数分别为38 nM和31 nM。（摘要截断于250字）
