RRC ID 18980
Author Aita Y, Kasahara T, Isobe K, Kawakami Y, Takekoshi K.
Title Effect of urotensin II on PC12 rat pheochromocytoma cells.
Journal J Neuroendocrinol
Abstract Urotensin II (U-II), initially identified as a cyclic peptide from fish urophysis, acts both as a strong vasoconstrictor and vasodilator in the vasculature via its receptor, G-protein coupled receptor 14. In addition, U-II and its receptor are co-expressed in the adrenal medulla, as well as in human pheochromocytomas, suggesting that this peptide may have some function in chromaffin cells. However, the precise role of U-II in these cells is unknown. In the present study, we initially demonstrate that U-II and its receptors mRNA are co-expressed in the rat pheochromocytoma cell line PC12. Moreover, U-II has not effect on tyrosine hydroxylase (TH), the rate-limiting enzyme involved in the biosynthesis of catecholamine, in terms of enzyme activity or at the mRNA level. However, U-II does induce an increase in the phosphorylation of TH specifically at Ser31 without affecting phosphorylation at the two other sites (Ser19 and Ser40). U-II also markedly activates extracellular signal-regulated kinases (ERKs) and p38, but not Jun N-terminal kinase. Blockade of the epidermal growth factor (EGF) receptor by AG1478 significantly reduces activation of ERK, suggesting that EGF receptor transactivation could act upstream of the ERK pathway in PC12 cells. Furthermore, U-II significantly increases dopamine secretion from PC12 cells. Finally, we show that U-II induced significant DNA synthesis in a ERKs and P38 mitogen-activated protein kinase-dependent manner. The results obtained indicate that U-II may exert its effects as a neuromodulator in chromaffin cells.
Volume 22(2)
Pages 83-91
Published 2010-2-1
DOI 10.1111/j.1365-2826.2009.01944.x
PMID 20025629
MeSH Amino Acid Sequence Animals Cell Proliferation Chromaffin Cells / drug effects Chromaffin Cells / enzymology Chromaffin Cells / metabolism* DNA / biosynthesis DNA / metabolism Dopamine / metabolism Enzyme Inhibitors / pharmacology ErbB Receptors / antagonists & inhibitors ErbB Receptors / metabolism Extracellular Signal-Regulated MAP Kinases / metabolism JNK Mitogen-Activated Protein Kinases / metabolism PC12 Cells Phosphorylation Quinazolines RNA, Messenger / metabolism Rats Receptors, G-Protein-Coupled / metabolism Tyrosine 3-Monooxygenase / genetics Tyrosine 3-Monooxygenase / metabolism Tyrphostins / pharmacology Urotensins / metabolism* p38 Mitogen-Activated Protein Kinases / metabolism
IF 2.886
Times Cited 8
Human and Animal Cells PC-12(RCB0009)