Zhang L, Dyer D C
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Iowa State University, Ames.
J Pharmacol Exp Ther. 1990 Jun;253(3):1236-44.
5-Hydroxytryptamine (5-HT) and 2,5-dimethoxy-4-methyl-amphetamine (DOM) are potent agonists on isolated ovine uterine arteries in late pregnancy. Similar pA2 values (8.56 and 8.33, respectively) of ketanserin, tested against 5-HT and DOM, indicate that responses produced by both agonists are mediated by the 5-HT2 receptor. The contractions produced by 8-OH-DPAT and 2-methyl-5-HT were also blocked by ketanserin (10(-8) M) with the dissociation constants (KB) being 2.49 and 2.88 nM, respectively. This provides evidence that these agonists are activating 5-HT2 receptors in the ovine uterine artery. DOM was more potent than 5-HT, but had a similar efficacy to that of 5-HT. The greater affinity of DOM may explain its greater potency. The dissociation constants (KA) of 5-HT and DOM acting on 5-HT receptors were determined by analysis of concentration-response data before and after fractional inactivation of receptors with dibenamine. The mean KA values for 5-HT and DOM were 3.7 +/- 0.7 x 10(-7) and 1.8 +/- 0.3 x 10(-7) M, respectively. Assessment of receptor occupancy vs. functional response demonstrated little or no receptor reserve in this tissue. Several other 5-HT receptor agonists caused contractions but were much less potent than 5-HT. The order of potency of these agonists was determined to be DOM greater than 5-HT greater than or equal to alpha-methyl-5-HT much greater than 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) greater than 2-methyl-5-HT greater than 1-(3-chlorophenyl) piperazine (mCPP) greater than m-trifluoromethyl-phenylpiperazine (TFMPP).(ABSTRACT TRUNCATED AT 250 WORDS)
5-羟色胺（5-HT）和2,5-二甲氧基-4-甲基苯丙胺（DOM）是妊娠晚期绵羊离体子宫动脉的强效激动剂。用酮色林分别对抗5-HT和DOM测试时，其相似的pA2值（分别为8.56和8.33）表明，两种激动剂产生的反应均由5-HT2受体介导。8-OH-DPAT和2-甲基-5-HT产生的收缩也被酮色林（10⁻⁸ M）阻断，解离常数（KB）分别为2.49和2.88 nM。这证明这些激动剂正在激活绵羊子宫动脉中的5-HT2受体。DOM比5-HT更有效，但效力与5-HT相似。DOM更高的亲和力可能解释了其更强的效力。通过对用苄胺部分灭活受体前后的浓度-反应数据进行分析，确定了5-HT和DOM作用于5-HT受体的解离常数（KA）。5-HT和DOM的平均KA值分别为3.7±0.7×10⁻⁷和1.8±0.3×10⁻⁷ M。受体占有率与功能反应的评估表明，该组织中几乎没有或没有受体储备。其他几种5-HT受体激动剂也引起收缩，但效力远低于5-HT。这些激动剂的效力顺序确定为DOM＞5-HT≥α-甲基-5-HT＞＞8-羟基-二丙基氨基四氢萘（8-OH-DPAT）＞2-甲基-5-HT＞1-（3-氯苯基）哌嗪（mCPP）＞间三氟甲基苯基哌嗪（TFMPP）。（摘要截断于250字）
