Structures and Functions of Prostaglandin Receptors

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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.