Cushing D J, Cohen M L
Cardiovascular Research, Lilly Research Laboratories Eli Lilly and Company, Indianapolis, Indiana.
J Pharmacol Exp Ther. 1992 Jun;261(3):856-62.
Serotonin (5-HT) is one important mediator of the coronary vasospasm and occlusion associated with thrombosis and atherosclerosis. 5-HT concentration-dependently contracted both canine and porcine coronary artery rings in vitro. In the dog, 5-HT-induced contraction was not blocked by either LY53857 (1 microM) or ketanserin (1 microM), but was blocked by the nonselective 5-HT receptor antagonist 1-naphthylpiperazine (1-NP) (100 nM), indicating 5-HT receptor involvement. Unlike the dog, both LY53857 (1 microM) and ketanserin (30 nM) antagonized 5-HT-induced contraction in pig arteries. Dissociation constants for LY53857 and ketanserin in porcine arteries were compared with those in rat jugular vein, a tissue possessing a well characterized 5-HT2 receptor. Both LY53857 (3 nM) and ketanserin (3 nM) antagonized 5-HT-induced contraction in rat jugular vein; however, the affinities of LY53857 and ketanserin in the rat jugular vein were significantly higher than those in the pig coronary. The rank order contractile potency for 5-HT, (alpha Me-5-HT) and sumatriptan in porcine coronary artery was consistent with that established for a 5-HT2 receptor, whereas the rank order potency in canine coronary artery indicated non-5-HT2 receptor involvement. Sumatriptan, a 5-HT1D receptor-selective agonist, was equieffective to 5-HT in contracting the canine coronary artery, a response inhibited by 1-NP (100 nM). Sumatriptan failed to contract either the pig coronary or rat jugular vein. In summary, significant differences exist in the 5-HT receptors that mediate contraction between the canine and porcine coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)
血清素(5-羟色胺,5-HT)是与血栓形成和动脉粥样硬化相关的冠状动脉痉挛和闭塞的一种重要介质。5-HT在体外能使犬和猪的冠状动脉环产生浓度依赖性收缩。在犬类中,LY53857(1微摩尔)或酮色林(1微摩尔)均不能阻断5-HT诱导的收缩,但非选择性5-HT受体拮抗剂1-萘基哌嗪(1-NP)(100纳摩尔)可阻断,表明有5-HT受体参与。与犬类不同,LY53857(1微摩尔)和酮色林(30纳摩尔)均可拮抗猪动脉中5-HT诱导的收缩。将LY53857和酮色林在猪动脉中的解离常数与在大鼠颈静脉(一种具有特征明确的5-HT2受体的组织)中的解离常数进行比较。LY53857(3纳摩尔)和酮色林(3纳摩尔)均可拮抗大鼠颈静脉中5-HT诱导的收缩;然而,LY53857和酮色林在大鼠颈静脉中的亲和力显著高于在猪冠状动脉中的亲和力。5-HT、α-甲基-5-HT和舒马曲坦在猪冠状动脉中的收缩效力排序与针对5-HT2受体确定的排序一致,而在犬冠状动脉中的效力排序表明无5-HT2受体参与。舒马曲坦是一种5-HT1D受体选择性激动剂,在使犬冠状动脉收缩方面与5-HT等效,该反应可被1-NP(100纳摩尔)抑制。舒马曲坦未能使猪冠状动脉或大鼠颈静脉收缩。总之,介导犬和猪冠状动脉收缩的5-HT受体存在显著差异。(摘要截短于250字)