| Project/Area Number |
10218206
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Miyazaki Medical College |
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Principal Investigator |
WADA Akihiko Miyazaki Medical College, Department of Pharmacology, Professor, 医学部, 教授 (30131949)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOO Hiroki Miyazaki Medical College, Department of Pharmacology, Instructor, 医学部, 助手 (30332894)
YANAGITA Toshihiko Miyazaki Medical College, Department of Pharmacology, Instructor, 医学部, 助手 (60295227)
KOBAYASHI Hideyuki Miyazaki Medical College, Department of Pharmacology, Associate Professor, 医学部, 助教授 (40148953)
UEZONO Yasuhito Nagasaki University, Medical School, Department of Pharmacology, Assistant Professor, 医学部, 講師 (20213340)
YAMAMOTO Ryuichi Kyushu University of Health and Welfare, Department of Pharmacology, Professor, 保健学部, 教授 (10094111)
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| Project Period (FY) |
1998 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥57,800,000 (Direct Cost: ¥57,800,000)
Fiscal Year 2002: ¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2001: ¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2000: ¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 1999: ¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1998: ¥12,300,000 (Direct Cost: ¥12,300,000)
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| Keywords | Bioactive peptide / Receptor / Gene expression / Brain microvessel endothelial cell / Glia cell / Vascular smooth muscle cell / Pregnant uterus / Adrenomedullin / PAMP / CRLR / RAMP / Adrenal chromaffin cells / Microvessels / Choroid plexus / Oligodendroglial cells / Adrenomedullin family / Uterus / Exocytosis / Tyrosine hydroxylase / Nicotinic receptors / Autocrine regulation / Brain microvessels / Catecholamine |
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| Research Abstract |
1) Analysis of adrenomedullin (AM) receptors, calcitonin gene-related peptide (CGRP) receptors and amylin receptors :
AM, CGRP and amylin are structurally homologus and they have similar physiological functions. However, receptors for these peptides have not well characterized. We studied receptors for these peptides in oligodendroglia KG1C cells. KG1C cells express caltitonin receptor-likereceptor (CRLR), receptor-activity-mocdifing protein (RAMP)-1, -2 and -3. We foundthat-AM acted on AM receptors (CRLR+RAMP-2, CRLR+RAMP-3) and CGRP1 receptors (CRLR+RAMP-1), CGRP acted on CGRP1 receptors and CGRP2 receptors, and amylin acted of CGRP1 receptors.
2) Synthesis and secretion of AM and its receptors in brain microvessels and glial cells :
Brain micovessels secreted AM into the brain parenchyma and the luminal side of the vessels, and the level of AM secreted to the luminal side of the vessels was one order higher than that reported previously. AM secretion from the brain microvessels was not
… More
stimulated by thrombin, lipopolysaccalide or cytokines differently form the secretion by the endotheial cells of peripheral vessels. However, the AM secretion to the luminal side was stimulated by the soluble factors derived from astrocytes. Endothelial cells and pericytes of brain microvessels expressde CRLR and RAMP-2 and -3, and AM stimulated CAMP production in these cells. In addition, we found that AM activated blood-brain barrier function by regulating p-glycoprotein, pinocytosis and integrity of tight junction of microvessels.
3) Maintenance of pregnancy by AM and AM receptors :
CRLR and RAMP-1 and -2 were expressed in the pregnant rat uterus. Expression of AM increased at the site of uterus attached to the placenta but not at the site not attached to the placenta or in the chorion. Uterus strip where the placenta was attached did not contract spontaneously, but began to contract periodically by the addition AM receptor antagonist, AM(22-52). These results suggest that AM and AM preceptors are involved in the maintenance of pregnancy by inhibiting the contraction of the uterus.
4) Mechanism of dilatation of iris sphincter muscle :
AM acted on AM preceptors and CGRP1 receptors in an autocrine/paracrine manner, and dilated the iris sphincter muscle by increasing NO and cAMP level. Less
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