2007 Fiscal Year Final Research Report Summary
Molecular Mechanisms of Prostaglandin Receptor-mediated Actions
| Project/Area Number |
18390023
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
SUGIMOTO Yukihiko Kyoto University, Graduate School of Pharmaceutical Sciences, Associate Professor (80243038)
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| Project Period (FY) |
2006 – 2007
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| Keywords | prostaglandins / prostanoid receptors / fever generation / fertilization / mucous protection of gut / ductus arteriosus / cumulus cells / cyclooxygenases |
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| Research Abstract |
The purpose of this study is to understand the molecular mechanisms underlying prostanoid-induced and prostanoid receptor-mediated physiological actions.
(1) Prostaglandin E_2 (PGE_2) plays a primary role in maintaining the patency of the ductus arteriosus (DA). EP4 deficiency, however, paradoxically results in fatal patent DA in mice. We found that EP4-mediated signals promote DA closure by hyaluronic acid (HA)-mediated intimal cushion formation. Chronic EP4 stimulation enhanced migration and HA production in DA smooth muscle cell, and activation of EP4 and protein kinase A increased HA Synthase (HAS)-2 transcripts. In immature rat DA explants, intimal cushion formation was promoted by EP4 stimuli. HAS2 gene transfer was sufficient to induce intimal cushion formation in EP4-deficient DA explants. Thus, EP4 has two essential roles in DA development, vascular dilation and intimal cushion formation. The latter action presumably facilitates luminal narrowing leading to adhesive occlusion a
… More
nd permanent closure of the vascular lumen.
(2) PGE_2 has been shown to produce fever by acting on EP3 receptors within preoptic area of the brain. However, there is little information about the molecular events downstream of EP3 activation in preoptic neurons. As a first step to approach this issue, we examined PGE_2-induced gene expression changes at single cell resolution in preoptic neurons expressing EP3. Microarray analysis of EP3-positive neurons indicated that gene expression of gamma-aminobutyric acid type A receptor (GABA_A) is decreased upon PGE_2 injection. Indeed, most EP3-positive neurons in the preoptic area are positive for the GABA_A. PGE_2 decreased the preoptic gene expression of GABA_A via EP3-dependent and pertussis toxin-sensitive pathway. PGE_2 attenuated the preoptic protein expression of GABA_A in wild-type but not in EP3-deficient mice. Thus, PGE_2-EP3 signaling elicits G_<i/o> activation in preoptic thermocenter neurons and a rapid decrease in preoptic GABA_A expression may be involved in PGE_2-induced fever. Less
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[Journal Article] Prostaglandin E_2 attenuates preoptic expression of GABA_A receptors via EP3 receptors.2008
Author(s)
Tsuchiya, H., Oka, T., Nakamura, K., Ichikawa, A., Saper, C. B., and Sugimoto, Y.
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Journal Title
J. Biol. Chem. 283
Pages: 11064-11071
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Prostaglandin I_2 plays a key role in zymosan-induced mouse pleurisy.2008
Author(s)
Yuhki, K. I., Ushikubi, F., Naraba, H., Ueno, A., Kato, H., Kojima, F., Narumiya, S., Sugimoto, Y., Matsushita, M., and Oh-Ishi, S.
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Journal Title
J. Pharmacol. Exp. Ther. (印刷中)
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Infusion of oxytocin induces successful delivery in prostanoid FP-receptor-deficient mice.2008
Author(s)
Kawamata, M., Yoshida, M. Sugimoto, Y., Kimura, T., Tonomura, Y., Takayanagi, Y., Yanagisawa, T., and Nishimori, K.
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Journal Title
Mol. Cell. Endocrinol. 283
Pages: 32-37
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Involvement of prostaglandin E2 in production of amyloid-peptides both in vitro and in vivo.2007
Author(s)
Hoshino, T., Nakaya, T., Homan, T., Tanaka, K., Sugimoto, Y., Araki, W., Narita, M., Narumiya, S., Suzuki, T., and Mizushima, T.
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Journal Title
J. Biol. Chem. 282
Pages: 32676-32688
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Oxytocin-induced phasic and tonic contractions are modulated by the contractile machinery rather than the quantity of oxytocin receptor.2007
Author(s)
Kawamata, M., Tonomura, Y., Kimura, T., Sugimoto, Y., Yanagisawa, T., and nishimori, K.
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Journal Title
Am. J. Physiol. Endocrinol. metab. 292
Pages: E992-E999
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Chronic activation of the prostaglandin receptor EP4 promotes hyaluronan-mediated neointimal formation in the ductus arteriosus.2006
Author(s)
Yokoyama, U., Minamisawa, S., Hong, Q., Ghatak, S., Akaike, T., Segi-Nishida, E., Iwasaki, S., Iwamoto, M., Misra, S., Tamura, K., Hori, H., Yokota, S., Toole, B. P., Sugimoto, Y., and Ishikawa, Y.
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Journal Title
J. Clin. Invest. 116
Pages: 3026-3034
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] Reduction of aquaporin-8 on fetal membranes under oligohydramnios in mice lacking prostaglandin F2 alpha receptor.2006
Author(s)
Shioji, M., Fukuda, H., Kanzaki, T., Wasada, K., Kanagawa, T., Shimoya, K., Mu, J., Sugimoto, Y., Murata, Y.
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Journal Title
J. Obstet. Gynaecol. Res. 32
Pages: 373-378
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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