RRC ID 12167
Author Takekoshi K, Ishii K, Isobe K, Nomura F, Nammoku T, Nakai T.
Title Effects of natriuretic peptides (ANP, BNP, CNP) on catecholamine synthesis and TH mRNA levels in PC12 cells.
Journal Life Sci
Abstract Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are present in adrenal chromaffin cells, and are co-secreted with catecholamines suggesting that these natriuretic peptides (NPs) may modulate functions of chromaffin cells in an autocrine and/or paracrine manner. Therefore, we investigated the effects of NPs on tyrosine hydroxylase (TH: a rate-limiting enzyme in biosynthesis of catecholamine) mRNA in rat pheochromocytoma PC12 cells. It was also determined whether the cyclic GMP/cGMP-dependent protein kinase (cGMP/PKG) pathway was involved in theses effects. Finally, we examined the effects of NPs on intracellular catecholamine content to confirm increase of catecholamine synthesis following TH mRNA induction. NPs (0.1 microM) induced significant increases of the TH mRNA (ANP= BNP> CNP). Also, the effects of NPs on TH mRNA were mimicked by 8-bromo cyclic GMP (1mM), and were blocked by KT5823 (1 microM) (inhibitor PKG) or LY83583 (1 microM) (guanylate cyclase inhibitor). Moreover, NPs were shown to induce significant increases of intracellular catecholamine contents (ANP= BNP> CNP). These findings suggest that NPs induced increases of TH mRNA through cGMP/PKG dependent mechanisms, which, in turn, resulted in stimulation of catecholamine synthesis in PC12 cells.
Volume 66(22)
Pages PL303-11
Published 2000-4-21
DOI 10.1016/s0024-3205(00)00549-x
PII S002432050000549X
PMID 10834306
MeSH Animals Atrial Natriuretic Factor / pharmacology* Catecholamines / biosynthesis* Cyclic GMP / analogs & derivatives Cyclic GMP / metabolism Cyclic GMP / pharmacology Cyclic GMP-Dependent Protein Kinases Enzyme Inhibitors / pharmacology Guanylate Cyclase / antagonists & inhibitors Natriuretic Peptide, Brain / pharmacology* Natriuretic Peptide, C-Type / pharmacology* PC12 Cells Protein Kinase Inhibitors Protein Kinases / metabolism RNA, Messenger / metabolism Rats Tyrosine 3-Monooxygenase / genetics Tyrosine 3-Monooxygenase / metabolism*
IF 3.647
Times Cited 19
DNA material pHTH1 Human tyrosine hydroxylase type I cDNA (RDB01269)
Human and Animal Cells PC-12(RCB0009)