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心脏组胺H3受体的发现、功能、定位、及其信号转导系统的研究

A Study of Cardiac Histamine H3 Receptors on Its Finding, Function, Location and Possible Signalline Transduction System

【作者】 罗晓星

【导师】 秦伯益; 谭月华;

【作者基本信息】 第四军医大学 , 药理学, 1993, 博士

【摘要】 组胺是迄今人类认识的人体内最古老,最具广泛生理,病理效应的自身活性物质。近一百年来,对其研究经久不衰,日益深入。组胺受体是介导组胺生物效应必不可少的重要环节。每一种组胺受体亚型的发现,以及对其分布和作用规律的认识,往往导致组胺受体药理学研究领域的一次大突破。 自从1983年Arrang首次报道,发现组胺受体新亚型—H3受体,以及1987年研制出选择性H3受体激动剂和拮抗剂以来,人们对于组胺H3受体的分布,功能,及其信号转导系统等方面的研究,表现了极大的兴趣和研究热情。现已发现,组胺H3受体,不仅广泛分布于脑内,而且广泛分布于外周交感,副交感,以及NCNA神经末梢突触前膜,调节神经递质的释放。因此,组胺H3受体可能是一类广泛分布于中枢和外周器官,并对器官功能具有重要调节作用的组胺受体新亚型。深入开展对H3受体分布,功能,作用规律,及其介导效应的分子机制的研究,不仅具有重要的理论意义,而且还可能导致一类作用于组胺H3受体的新型药物问世。 心脏组胺含量丰富,而且也是组胺作用的重要靶器官之一,对于组胺是否参予调节心交感神经释放递质了解甚少,心脏是否分布有H3受体,也不见报道。本课题着重对心脏H3受体的功能,分布,定位进行研究,并初步探索H3受体信号转导系统。

【Abstract】 The recognition of histamine as an autacoid in regulating the functions of many organs in human body started at the beginning of this century. Since then, research interest in the receptors that mediated the pharmacological actions of this biogenic amine has waxed and reached a peak when a new subtype of histamine receptor has been announced. In 1983 a paper from the research group of Schwartz, for the first time, showed that histamine mediated inhibition of its own release from slices of cerebral cortex through a new subtype of histamine receptor-H3-receptor. Subsequently, the most potent and selective H3-receptor agonist and antagonist were discribed by the same author in 1987, which further confirmed the existance of H3-receptors. Now, an research interest in H3receptor research is on the increase, which includes studies on its distribution, function, location and the intracellular signaling processes involved. It has substantially been show

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