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。应激对经固定化的脑肌素2（UCN-2）表达的影响，在2hr固定末期，在PVN的副细胞部分中表现出UCN 2 mRNA表达的戏剧性诱导。相反，缺水3天诱导的UCN-2 mRNA表达主要在PVN的大细胞部分中。双标记原位杂交揭示了UCN 2 mRNA在固定固定后，大约45％的CRH mRNA mRNA表达MRNA的表达细胞在PVN的副细胞部分中或在大多数加压蛋白表达mRNA mRNA mRNA depraptribriart depravectiond的磁性细胞中的共定位。下丘脑CRH和AVP表达以及血浆ACTH的UCN-2和UCN-3。 AVP和皮质酮分泌1）ICV UCN-2ICV施用UCN-2（7.5μg）在5-15分钟时导致血浆ACTH升高。它在下丘脑室室核（PVN）中分别增加了15分钟和在给药后15-30分钟的CRH异核（HN…更多）RNA和C-FOS mRNA的表达。 AVP HNRNAIN的表达在ICV UCN-2.2之后的PVN和上核（SON）的巨细胞部分没有变化，UCN-3ICV给药UCN-3（7.5μg）刺激血浆ACTH和在5-30分钟的刺激血浆ACTH和皮质酮分泌，并在5-30分钟和后15-30分钟。它还在下丘脑PVN中分别刺激了CRH HNRNA和C-FOS mRNA表达，分别在给药后15-30分钟。 ICV UCN-3在5分钟时引起血浆AVP升高。然而，AVP HNRNA在PVN和上核的大细胞部分中的表达（SON）在ICV UCN-3给药后没有变化。3）ICV给药非特异性CRH受体拮抗剂α-螺旋α-螺旋α-螺旋α-螺旋α-helicalical Crf 9-41（ahc）和特定的CRHR2拮抗剂 - AS-ANT-330（AS）AS-AS-330（ASV）ASING-330（ASV）分泌。施用αHC或ASV-30抑制UCN-2和UCN-3诱导的血浆ACTH分泌。3.ConconclusionTheseThess结果表明，UCN-2通过CRHR2刺激CRH-ACTH分泌，并且UCN-2和UCN-3可能至少参与压力诱导的Acth分泌。较少的