title: Urocortin stimulates tyrosine hydroxylase activity via the cAMP/protein kinase a pathway in rat Pheochromocytoma PC12 cells.
abstract: Urocortin is a novel mammalian member of the corticotrophin releasing factor (CRF)-related peptides. We have investigated the expression, mechanism of action and second messenger for urocortin in rat pheochromocytoma PC12 cells. We initially confirmed the expression of urocortin and CRF-R2beta, which is thought to be an endogenous receptor for urocortin, in PC12 cells. We also demonstrate that urocortin (> or = 1 nM) significantly elevates the level of cAMP in these cells. Moreover, alpha-helical CRF-(9-41), a more specific antagonist of CRF-R2 than CRF-R1 and the adenylate cyclase inhibitor SQ22536, inhibited the urocortin-induced increase in the level of cAMP. Thus, urocortin may exert its physiological role in chromaffin cells via CRF-R2beta coupling to adenylate cyclase. Urocortin (> or = 1 nM) significantly increased the mRNA level and activity of tyrosine hydroxylase (TH), a rate-limiting enzyme in the biosynthesis of catecholamine. Furthermore, urocortin-induced changes in TH-mRNA and activity were inhibited by H89 (a PKA inhibitor) and SQ22536 as well as alpha-helical CRF-(9-41). However, urocortin did not affect DNA synthesis or catecholamine secretion in these cells. In conclusion, we have demonstrated that urocortin stimulates catecholamine biosynthesis via the cAMP/protein kinase A pathway in PC12 cells, where both urocortin and its receptor, CRF-R2, are expressed.
authors.affiliation: Department of Clinical Pathology, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nanmoku
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takekoshi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukuda
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Isobe
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Shibuya
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawakami
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D015290:Second Messenger Systems / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D054832:Urocortins
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D002395:Catecholamines; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D054832:Urocortins; C017759:9-(tetrahydro-2-furyl)-adenine; D004247:DNA; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D000225:Adenine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide