Cataldi Mauro, Borriello Francesco, Granata Francescopaolo, Annunziato Lucio, Marone Gianni
Department of Neuroscience, Reproductive and Odontostomatologic Sciences, University of Naples Federico II, Naples, Italy.
Chem Immunol Allergy. 2014;100:214-26. doi: 10.1159/000358740. Epub 2014 May 22.
The synthesis and the identification of histamine marked a milestone in both pharmacological and immunological research. Since Sir Henry Dale and Patrick Laidlaw described some of its physiological effects in vivo in 1910, histamine has been shown to play a key role in the control of gastric acid secretion and in allergic disorders. Using selective agonists and antagonists, as well as molecular biology tools, four histamine receptors (H1R, H2R, H3R and H4R) have been identified. The Nobel Prize in Physiology and Medicine was awarded to Daniel Bovet in 1957 for the discovery of antihistamines (anti-H1R) and to Sir James Black in 1988 for the identification of anti-H2R antagonists. Anti-H1R and anti-H2R histamine receptor antagonists have revolutionized the treatment of certain allergic disorders and gastric acid-related conditions, respectively. More recently, anti-H3R antagonists have entered early-phase clinical trials for possible application in obesity and a variety of neurologic disorders. The preferential expression of H4R by several immune cells and its involvement in the development of allergic inflammation provide the rationale for the use of anti-H4R antagonists in allergic and in other immune-related disorders.
组胺的合成与鉴定在药理学和免疫学研究中都具有里程碑意义。自1910年亨利·戴尔爵士和帕特里克·莱德劳描述了组胺在体内的一些生理作用以来，组胺已被证明在胃酸分泌控制和过敏性疾病中起关键作用。通过使用选择性激动剂和拮抗剂以及分子生物学工具，已鉴定出四种组胺受体（H1R、H2R、H3R和H4R）。1957年，丹尼尔·博韦因发现抗组胺药（抗H1R）而被授予诺贝尔生理学和医学奖，1988年，詹姆斯·布莱克爵士因鉴定出抗H2R拮抗剂而获奖。抗H1R和抗H2R组胺受体拮抗剂分别彻底改变了某些过敏性疾病和胃酸相关疾病的治疗方法。最近，抗H3R拮抗剂已进入早期临床试验，可能用于治疗肥胖症和多种神经系统疾病。几种免疫细胞对H4R的优先表达及其在过敏性炎症发展中的作用，为在过敏性疾病和其他免疫相关疾病中使用抗H4R拮抗剂提供了理论依据。
