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Structures and Functions of Prostaglandin Receptors

前列腺素受体的结构和功能

基本信息

批准号：
05454568
负责人：
ICHIKAWA Atsushi
金额：
$ 4.35万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454568/
关键词：
prostaglandin receptor PGE2 receptor PGI2 receptor G protein PGF2alpha receptor アデニル酸シクラーゼホスホリパーゼC G蛋白共役 EP3イソフォームプロスタグランジンI_2 cDNA プロスタグランジンE_2 情報伝達系腎臓 Northern blotting

项目摘要

Prostaglandins exist a wide spectrum of physiological and pharmacological actions through interaction to their specific receptors on plasma membranes in diverse tissues . In order to the clarify the molecular actions of prostaglandins, it needs to clone their cDNAs and studied the structures and functions of their receptors in expressed cells. In this project, we have cloned cDNAs for mouse PGE2 receptor, PGF2alpha receptor and PGI2 receptor. The cloned mouse PGE2 receptor consisted of three different subtypes, EP1, EP2 and EP3. The cloned three receptor subtypes are coupled to Ca^<2+> mobilization, and stimulation and inhibition of adenylate cyclase, respectively. The three subtypes show different tissue distributions, EP1 is mainly expressed in kidney, EP2 in thymus and ileum, and EP3 in uterus and kidney. In addition, we have identified three isoforms of mouse EP3, which are produced through alternative splicing and differ in their carboxy-terminal tails. These isoforms differ in the efficiency of G protein activation or in the specificity of coupling to G proyeins. The cDNAs for the mouse PGF2alpha and human PGI2 receptors have cloned and expressed in mammalian cells. The PGF2alpha receotor which is coupled to Ca^<2+> mobilization is abundantly expressed in pregnant ovary and smooth muscle, and PGI2 receptor which coupled to both adenylate cyclase and phosphatydyl inositol metabolism is noted to abundantly express in thymus. This molecular characterization is useful for understanding the diverse physiological roles of prostaglandins.

前列腺素通过与不同组织质膜上的特定受体相互作用，具有广泛的生理和药理作用。为了阐明前列腺素的分子作用，需要克隆前列腺素的cDNA，并研究其受体在表达细胞中的结构和功能。在本项目中，我们克隆了小鼠PGE2受体、PGF2Alpha受体和PGI2受体的cDNA。克隆的小鼠PGE2受体由EP1、EP2和EP3三种不同亚型组成。克隆的三种受体亚型分别偶联于Ca~(2+)动员和腺苷环化酶的刺激和抑制。EP1主要表达于肾脏，EP2主要表达于胸腺和回肠，EP3主要表达于子宫和肾脏。此外，我们还鉴定了小鼠EP3的三种异构体，它们是通过选择性剪接产生的，它们的羧基末端尾巴不同。这些异构体在G蛋白激活的效率或与G蛋白偶联的特异性上存在差异。小鼠PGF2pha和人PGI2受体的cDNA已被克隆并在哺乳动物细胞中表达。与Ca~(2+)和Gt~(2+)动员偶联的PGF2α受体在妊娠卵巢和平滑肌中大量表达，而与腺苷环化酶和磷脂酰肌醇代谢偶联的PGI_2受体在胸腺中也大量表达。这种分子特征有助于理解前列腺素的不同生理作用。