Ohtsu Hiroshi, Watanabe Takehiko
Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Biochem Biophys Res Commun. 2003 Jun 6;305(3):443-7. doi: 10.1016/s0006-291x(03)00696-x.
Gene targeting techniques have revolutionized the investigation of the effects of bioactive substances in pathological and physiological conditions. Histamine synthesis is uniquely catalyzed by L-histidine decarboxylase. The knockout mice of this gene express no histamine-producing activity and lack histamine. These mice have been used to examine the mechanisms of histamine in several known phenotypes, e.g., gastric acid secretion, contraction of smooth muscles, vascular permeability, and awakening, and have also been used to explore unreported effects of histamine in the whole body. First, we will review the former mechanisms and then move to the latter, new effects. Especially, in the latter mechanisms, we focus on several important roles of histamine in angiogenesis, neutrophil and eosinophil recruitment, bacterial infection, and systemic anaphylaxis in this review. Moreover, to our surprise, the morphology of mast cells in the knockout mice was severely affected by the absence of histamine in terms of their granules.
基因靶向技术彻底改变了对生物活性物质在病理和生理条件下作用的研究。组胺的合成由L-组氨酸脱羧酶独特地催化。该基因的敲除小鼠不表达产生组胺的活性且缺乏组胺。这些小鼠已被用于研究组胺在几种已知表型中的作用机制，例如胃酸分泌、平滑肌收缩、血管通透性和觉醒，并且还被用于探索组胺在全身的未报道作用。首先，我们将回顾前者的机制，然后转向后者，即新的作用。特别是，在后者的机制中，在本综述中我们重点关注组胺在血管生成、中性粒细胞和嗜酸性粒细胞募集、细菌感染和全身性过敏反应中的几个重要作用。此外，令我们惊讶的是，敲除小鼠中肥大细胞的形态在其颗粒方面受到组胺缺乏的严重影响。
