Physiological role of CRH type 2 receptor and its endogenous ligands

1.应激对束缚大鼠脑内Ucn-2表达的影响：束缚2小时后，下丘脑室旁核小细胞部Ucn-2的表达明显增强。相反，缺水3d后，UCN-2mRNA的表达主要集中在PVN的大细胞部。双标记原位杂交显示，束缚后约45%的CRH表达细胞在下丘脑室旁核共表达UCN-2mRNA，或在缺水后大部分表达加压素mRNA的细胞共定位于PVN大细胞部。2.侧脑室注射UCN-2和UCN-3对下丘脑CRH和AVP表达及血浆ACTH的影响。(1)侧脑室注射UCN-2(7.5mgUCN-2)后，血浆促肾上腺皮质激素水平在5-15分钟内升高；增加促肾上腺皮质激素释放激素异核激素(hN…)的表达此外，下丘脑室旁核(PVN)在给药后15分钟和15-30分钟分别有核糖核酸和c-fos基因表达。(2)侧脑室注射UCN-3(7.5μg)刺激大鼠血浆促肾上腺皮质激素和皮质酮分泌的作用分别在给药后5-30min和15-30min。对下丘脑室旁核CRH hnRNA和c-FOS mRNA表达也有刺激作用，给药后15min和15min~30min分别可刺激CRH hnRNA和c-fos mRNA的表达。侧脑室注射UCN-3后5min血浆AVP水平升高。3)脑室注射非特异性CRH受体拮抗剂α-螺旋CRF9-41(αHC)和特异性CRH受体拮抗剂ACTH-30(ASV-30)对UCN-2诱导的促肾上腺皮质激素释放有影响。ICV注射αHC或ASV30可抑制UCN-2和UCN-3诱导的血浆促肾上腺皮质激素分泌。较少

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