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Physiological role of CRH type 2 receptor and its endogenous ligands

CRH 2型受体及其内源性配体的生理作用

基本信息

批准号：
15590980
负责人：
HASHIMOTO Kozo
金额：
$ 2.24万
依托单位：
Kochi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

1.Effect of stress on the expression of Urocortin 2(Ucn-2) in the brainRats subjected to immobilization exhibited a dramatic induction of Ucn 2 mRNA expression in the parvocellular part of the PVN at the end of 2hr immobilization. In contrast, water deprivation for 3 days induced Ucn-2 mRNA expression mainly in the magnocellular part of the PVN. Double-label in situ hybridization revealed colocalization of Ucn 2mRNA in approximately 45% of the CRH mRNA-expressing cells in the paravocellular part of the PVN following immobilization, or colocalization in most of the vasopressin mRNA-expressing mRNA-expressing cells in the magnocellular part of the PVN following water deprivation.2.Effect of intraventricular (icv) administration of Ucn-2 and Ucn-3 on hypothalamic CRH and AVP expression and plasma ACTH. AVP and corticosterone secretion1)Effect of icv Ucn-2Icv administration of Ucn-2 (7.5μg) caused an elevation of plasma ACTH at 5-15 min. It increased the expression of CRH heteronuclear (hn … More ) RNA and c-fos mRNA at 15 min and at 15-30 min after the administration, respectively, in the hypothalamic paraventricular nucleus(PVN). The expression of AVP hnRNAin the magnocellular part of PVN and supraoptic nucleus (SON) did not change after icv Ucn-2.2)Effect of Ucn-3Icv administration of Ucn-3 (7.5μg) stimulated plasma ACTH and corticosterone secretion at 5-30 min and at 15-30 min after the administration, respectively. It also stimulated CRH hnRNA and c-fos mRNA expression at 15 min and at 15-30 min after the administration, respectively, in the hypothalamic PVN. Icv Ucn-3 caused plasma AVP elevation at 5 min. However, the expression of AVP hnRNA in the magnocellular part of PVN and supraoptic nucleus (SON) did not change after icv Ucn-3 administration.3)Effect of icv administration of nonspecific CRH receptor antagonist α-helical CRF 9-41(αhC) and specific CRHR2 antagonist antigauvagine-30(ASV-30) on Ucn-2-induced ACTH secretion.Icv administration of αhC or ASV-30 inhibited Ucn-2-and Ucn-3-induced plasma ACTH secretion.3.ConclusionThese results suggest that Ucn-2 stimulates CRH-ACTH secretion via CRHR2 and that Ucn-2 and Ucn-3 maybe involved at least in part in stress-induced ACTH secretion. Less

1.应激对脑内Urocortin 2(Ucn-2)表达的影响进行固定的大鼠在2小时固定结束时表现出PVN细细胞部分Ucn 2 mRNA表达的显着诱导。相反，缺水3天主要在PVN的大细胞部分诱导Ucn-2 mRNA表达。双标记原位杂交显示，固定后，Ucn 2mRNA 共定位于 PVN 细胞旁细胞部分中约 45% 的 CRH mRNA 表达细胞中，或者缺水后，Ucn 2mRNA 共定位于 PVN 巨细胞部分中的大多数表达加压素 mRNA 的 mRNA 表达细胞中。 2. 心室内的影响 (icv)施用Ucn-2和Ucn-3对下丘脑CRH和AVP表达以及血浆ACTH的影响。 AVP 和皮质酮分泌 1) icv Ucn-2 的影响 Icv 施用 Ucn-2 (7.5μg) 引起血浆 ACTH 在 5-15 分钟升高。给药后 15 分钟和 15-30 分钟分别增加下丘脑室旁核 (PVN) 中 CRH 异核 (hn … More ) RNA 和 c-fos mRNA 的表达。 icv Ucn-2.2)Ucn-3后，PVN大细胞部分和视上核(SON)中AVP hnRNA的表达没有变化。Ucn-3的作用Icv施用Ucn-3(7.5μg)分别在施用后5-30分钟和15-30分钟刺激血浆ACTH和皮质酮分泌。它还分别在给药后15分钟和15-30分钟刺激下丘脑PVN中的CRH hnRNA和c-fos mRNA表达。 Icv Ucn-3 在 5 分钟时引起血浆 AVP 升高。然而，静脉注射Ucn-3后，PVN大细胞部分和视上核（SON）中AVP hnRNA的表达没有变化。3）静脉注射非特异性CRH受体拮抗剂α-螺旋CRF 9-41（αhC）和特异性CRHR2拮抗剂抗高瓦金-30（ASV-30）对Ucn-2诱导的ACTH的影响 Icv施用αhC或ASV-30抑制Ucn-2和Ucn-3诱导的血浆ACTH分泌。3.结论这些结果表明Ucn-2通过CRHR2刺激CRH-ACTH分泌，并且Ucn-2和Ucn-3可能至少部分参与应激诱导的ACTH分泌。较少的