RRC ID 12165
Author Takekoshi K, Ishii K, Kawakami Y, Isobe K, Nakai T.
Title kappa-Opioid inhibits catecholamine biosynthesis in PC12 rat pheochromocytoma cell.
Journal FEBS Lett
Abstract It was reported that nicotine-induced dopamine release in the rat pheochromocytoma cell line, PC12 cells, was inhibited by kappa-opioid. However, it is not known whether inhibition of catecholamine biosynthesis is involved in the inhibitory mechanisms of kappa-opioids in PC12 cells. U-69593 (a kappa-opioid agonist: >/=100 nM) significantly inhibited the nicotine-induced increase of tyrosine hydroxylase (TH, a rate-limiting enzyme in biosynthesis of catecholamine) enzyme activity and TH mRNA levels. These inhibitory effects were completely reversed by naloxone and nor-binaltorphimine dihydrochloride (nor-BNI), a specific kappa-antagonist, whereas pertussis toxin (PTX) only partially reversed this inhibitory effect. Also, U-69593 (>/=100 nM) significantly inhibited the nicotine-induced increase of cAMP production. This inhibitory effect was completely reversed by naloxone and nor-BNI, whilst only partially reversed by PTX. Moreover, U-69593 (>/=100 nM) significantly inhibited the nicotine-induced increase of both the TH protein level and intracellular catecholamine levels. These results indicate that the anti-cholinergic actions of kappa-opioid can be explained partially by its inhibition of both TH enzyme activity and TH synthesis, through suppression of the cAMP/protein kinase A pathway. It would also appear that the PTX-sensitive G-protein mediates the inhibitory effect of this pathway, at least in part.
Volume 477(3)
Pages 273-7
Published 2000-7-21
DOI 10.1016/s0014-5793(00)01789-0
PII S0014-5793(00)01789-0
PMID 10908734
MeSH Animals Benzeneacetamides* Catecholamines / antagonists & inhibitors* Catecholamines / biosynthesis Cyclic AMP / biosynthesis Nicotine / pharmacology Opioid Peptides / pharmacology* PC12 Cells Pyrrolidines / pharmacology RNA, Messenger / genetics Rats Receptors, Opioid, kappa / agonists Tyrosine 3-Monooxygenase / antagonists & inhibitors Tyrosine 3-Monooxygenase / genetics
IF 3.057
Times Cited 18
DNA material pHTH1 Human tyrosine hydroxylase type I cDNA (RDB01269)
Human and Animal Cells PC-12(RCB0009)