Physiological role of CRH type 2 receptor and its endogenous ligands

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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