Structures and Functions of Prostaglandin Receptors

前列腺素通过与不同组织质膜上的特异性受体相互作用而发挥广泛的生理和药理作用。为了进一步阐明其分子生物学作用，需要克隆其cDNA并研究其受体在表达细胞中的结构和功能。本研究克隆了小鼠前列腺素E_2受体、前列腺素F_（2 α）受体和前列腺素I_2受体的cDNA。克隆的小鼠PGE 2受体由三种不同的亚型组成，EP 1，EP 2和EP 3。克隆的三种受体亚型分别与Ca^<2+>动员、腺苷酸环化酶的刺激和抑制偶联。三种亚型的组织分布不同，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，我们已经确定了三种亚型的小鼠EP3，这是通过选择性剪接和不同的羧基末端尾巴。这些同种型在G蛋白活化的效率或与G蛋白偶联的特异性方面不同。小鼠PGF 2 α和人PGI2受体的cDNA已克隆并在哺乳动物细胞中表达。与Ca^2+动员偶联的PGF 2 α受体在妊娠卵巢和平滑肌中大量表达，与腺苷酸环化酶和磷酸肌醇代谢偶联的PGI2受体在胸腺中大量表达。这种分子表征对于理解野牡丹素的不同生理作用是有用的。

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.