2002 Fiscal Year Final Research Report Summary
Gene expression analysis of febrile neurons expressing prostaglandin receptor EPS
| Project/Area Number |
13672279
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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, 薬学研究科, 助教授 (80243038)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIKAWA Atsushi Kyoto University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (10025695)
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| Project Period (FY) |
2001 – 2002
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| Keywords | preoptic area / vasomotor center / GABA / receptor subtypes / single cell analysis / microarray / pyrogen / aspirin |
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| Research Abstract |
The purpose of this study is (1) to understand what genes are activated upon EP3 signaling in hypothalamic neurons, (2) to investigate signal transduction machanisms exerted by EPS in various cell types, and (3) to clarify which EP subtype is involved in particular pathophysiological actions of PGE2
(1) In order to characterize single cell gene expression profiles of hypothalamic EP3-positive neurons, we established and optimized single cell gene expression analysis method. By using this method, we characterized genes changes their expression levels upon PGE2 treatment. PGE2 reduced expression levels of various kinds of genes including GABA A receptors. It should be noted that a GABA agonist has been reported to block PGE2-induced febrile response. We proposed that down-regulation of GABA receptor might be a key event in EP3-expressiong neurons to elicit fever
(2) We identified upregulation of specific EP gene expression in immune, ovarian, epidermal, and mucosal tissues upon various kin
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(3) EP3 has been shown to be coupled to Gi activity, inhibition of adenylate cyclase. We found that EP3 receptors expressed in COS-7 cells showed augmentation of other receptor-stimulated Gs activity in an agonistdependent manner. This EP3 signaling may reflect some aspects of the physiological function of PGE2, such as pain sensation
(4) We found that EP2 deficiency attenuated intestinal polyp formation both in number and size in Apc KO mice. We introduced dextransulfate (DSS)induced colitis model into Epdeficient mice. As a result, only EP-4deficient mice showed severe colitis upon 3%DSS treatment thai did not induce significant colitisin wild-type mice. EP4 has been shown to promote epithelial regeneration and to inhibit activation of leukocytes and lymphocytes. We further found that EP3-deficient mice showed increased bleeding tendency and decreased susceptibility to arachidonateinduced thromboembolism compared with wild-type mice. EP3 appears to potentiate TP-induced platelet aggregation by increasing intracellular Ca2+ and/or decreasing cAMP level Less
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Research Products
(12 results)
