MOLECULAR AND FUNCTIONAL DIVERSITY OF HISTAMINE-RECEPTOR SUBTYPES
MOLECULAR AND FUNCTIONAL DIVERSITY OF HISTAMINE-RECEPTOR SUBTYPES
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DOI：
10.1111/j.1749-6632.1995.tb17489.x
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发表时间：
1995-01-01
期刊：
影响因子：
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通讯作者：
SCHWARTZ, JC
中科院分区：
文献类型：
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作者：
ARRANG, JM;DRUTEL, G;SCHWARTZ, JC
组胺的早期病史与过敏有很大关系。世纪初，亨利戴尔爵士和他的同事在从麦角提取物中分离出组胺后，描述了组胺的主要作用。也就是说，这些科学家发现了它对平滑肌的强收缩作用和它诱导的毛细血管扩张，这与过敏性休克的一些最初表现相似。他们还发现组胺存在于许多组织中，但另一位英国科学家Feldberg清楚地证明了过敏反应时组胺从肺中释放出来，并诱导了显著的支气管收缩。组胺通过与几种不同受体亚型相互作用发挥其各种生物学效应的想法主要是随着亚型选择性拮抗剂的设计而逐渐出现的。人们首先认识到，Bovet和Staub设计的第一种“抗组胺药”（现在称为HI受体拮抗剂）“不能均匀地阻断组胺的所有作用，例如，胃分泌不受影响。在此基础上以及激动剂的差异作用上，Ash和Schild 2明确地假定存在第二种受体亚型。H2受体的存在是通过设计一种选择性（非H1）拮抗剂布立米特以及几种相对选择性激动剂而明确确立的。3
The early history of histamine is largcly associatcd with allcrgy. The major actions of histamine were described at the beginning of this century by Sir Henry Dale and his colleagues after its isolation from ergot extracts. Namely, its potcnt contractile cffccts on smooth muscles and thc capillary dilation it induces, which mimic some initial manifestations of the anaphylactic shock, were identified by these scientists. They also detccted the presence of the aminc in many tissues, but it was another British scientist, Feldberg, who clearly demonstrated that histamine was released from the lung during the anaphylactic response and that it induccd a marked bronchoconstriction.The idea that histamine exerts its various biological effects via interaction with several distinct rcccptor subtypes progrcssively arose mainly with the design of subtype-selective antagonists. It was first realized that the “antihistamines”(now termed HI-receptor antagonists), the first of which were designed by Bovet and Staub,’did not block uniformly all actions of histamine, leaving, for instance, gastric secretion unaffccted. On this basis as well as on thc diffcrcntial action of agonists, Ash and Schild2 clearly postulated the existence of a second receptor subtype. The existence of the H2 receptor was definitively established with the design of burimamide, a selective (non-H1) antagonist, as well as of several relatively selective agonists. 3