RRC ID 42376
Author Nanmoku T, Takekoshi K, Fukuda T, Isobe K, Shibuya S, Kawakami Y.
Title Urocortin stimulates tyrosine hydroxylase activity via the cAMP/protein kinase a pathway in rat Pheochromocytoma PC12 cells.
Journal Neurosci Lett
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.
Volume 382(1-2)
Pages 124-7
Published 2005-7-1
DOI 10.1016/j.neulet.2005.02.069
PII S0304-3940(05)00272-7
PMID 15911134
MeSH Adenine / analogs & derivatives* Adenine / pharmacology Adenylyl Cyclase Inhibitors Animals Catecholamines / biosynthesis Catecholamines / metabolism Corticotropin-Releasing Hormone / biosynthesis Corticotropin-Releasing Hormone / metabolism Corticotropin-Releasing Hormone / pharmacology Corticotropin-Releasing Hormone / physiology* Cyclic AMP / physiology* Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases / physiology* DNA / biosynthesis Enzyme Inhibitors / pharmacology Isoquinolines / pharmacology PC12 Cells Rats Second Messenger Systems / physiology Sulfonamides / pharmacology Tyrosine 3-Monooxygenase / metabolism* Urocortins
IF 2.274
Times Cited 12
Human and Animal Cells PC-12(RCB0009)