| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Masaaki Gifu University, department of technology, progessor, 工学部, 教授 (90093046)
SAKAMOTO Kazuichi Osaka Bioscience Institute, 4th department, research scientist, 第4研究部, 研究員 (90235169)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Prostaglandin (PG) E_2 exerts diverse physiological and pharmacological actions such as vasodilatation, immunosuppression, and fever through PGE receptors ubiquitously distributed in the whole body. The PGE receptor is subdivided into three subtypes, EP1, EP2, and EP3, which are coupled to phosphoinositide metabolism, stimulation and inhibition of adenylate cyclase, respectively. Prostaglandins are a group of C_<20> carboxylic acids containing a cyclopentane ring. In addition to PGE_2, PDG_2, PGF_<2alpha>, and PGI_2 are known to produce their activities through their respective receptors. Because there are few agonists and antagonists which recognize the respective PG receptor, it is not always clear through which receptor a given PG elicits an action. To solve this problem, we carried out studies on identification and cloning of PG receptors and analysis of signal transduction and obtained following results. 1) PGI_2 receptor protein was identified by photoaffinity labeling with a synthetic stable PGI_2 analogue. 2) We cloned PGE receptor subtype EP1, which elevates the intracellular Ca^<2+> without stimulation of phosphoinositide metabolism. 3) Four isoforms of EP3 receptor exist in bovine adrenal medulla and they couple to different signal transduction through different GTP-binding proteins. 4) We succeeded in the cloning of PGF_<2alpha> receptor from bovine corpus luteum of the ovary and demonstrated the coupling of the receptor with G_q in cDNA-transfected Chinese hamster cells. 5) Both PGE_2 and PGF_<2alpha> involve pain transmission through glutamate receptors.
Recently, PGE receptor subtypes EP1, EP2, and EP3 and PGF_<2alpha> receptor have been successively cloned as thromboxane A_2 receptor cDNA as probe. We can expect to assign functional groups of PGs to activation of PG receptor proteins which produces information transfer to the effector in the near future.
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