Drummond A H, Bucher F, Levitan I B
J Biol Chem. 1980 Jul 25;255(14):6679-86.
d-[3H]Lysergic acid diethylamide (LSD) bound to both dopamine- and serotonin (5HT)-sensitive sites in a particulate fraction derived from the central nervous system of the snail Helix pomatia. Conditions were found which enabled the two sites to be studied independently. [3H]LSD appeared to have a slightly higher affinity for dopamine-sensitive binding (Kd = 0.5 nM) than for 5HT-sensitive binding (Kd = 1.2 nM). A pharmacological analysis of the binding indicated that while dopamine- and 5HT-related agonists clearly discriminated between the two sites, putative antagonists showed little specificity for dopamine- or 5HT-sensitive binding. The pharmacology of 5HR-sensitive [3H]LSD binding was studied in relation to a 5HT-sensitive adenylate cyclase present in a particulate fraction derived from the same tissue. There was a very good correlation between the abilities of a range of agents to act as agonists or antagonists in the 5HT-sensitive adenylate cyclase assay and their abilities to displace 5HT-sensitive [3H]LSD binding (r = 0.94; p less than 0.001). In particular, d-LSD and a number of neurologic drugs were inhibitory in both assays in a stereoselective manner. These data suggest that in molluscan tissues, 5HT-sensitive [3H]LSD binding is related to the 5HT receptor which is coupled to adenylate cyclase.
d-[3H]麦角酸二乙酰胺(LSD)与源自蜗牛Helix pomatia中枢神经系统的微粒体部分中的多巴胺敏感位点和5-羟色胺(5HT)敏感位点均有结合。发现了能使这两个位点得以独立研究的条件。[3H]LSD对多巴胺敏感结合(Kd = 0.5 nM)的亲和力似乎比对5HT敏感结合(Kd = 1.2 nM)略高。对该结合的药理学分析表明,虽然多巴胺相关和5HT相关激动剂能明确区分这两个位点,但假定的拮抗剂对多巴胺敏感或5HT敏感结合几乎没有特异性。针对存在于源自同一组织的微粒体部分中的5HT敏感腺苷酸环化酶,研究了5HT敏感的[3H]LSD结合的药理学。在5HT敏感腺苷酸环化酶测定中一系列试剂作为激动剂或拮抗剂的作用能力与其取代5HT敏感的[3H]LSD结合的能力之间存在非常良好的相关性(r = 0.94;p小于0.001)。特别是,d-LSD和一些神经药物在两种测定中均呈立体选择性抑制作用。这些数据表明,在软体动物组织中,5HT敏感的[3H]LSD结合与与腺苷酸环化酶偶联的5HT受体有关。