kappa-Opioid inhibits catecholamine biosynthesis in PC12 rat pheochromocytoma cell.
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.
Takekoshi
K
K
Department of Clinical Pathology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Ibaraki 305-8575, Tsukuba, Japan. k-takemd@md.tsukuba.ac.jp
Ishii
K
K
Kawakami
Y
Y
Isobe
K
K
Nakai
T
T
D000818:Animals; D044482:Benzeneacetamides; D002395:Catecholamines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000242:Cyclic AMP / Q000096:biosynthesis; D009538:Nicotine / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D016716:PC12 Cells; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000235:genetics
D044482:Benzeneacetamides; D002395:Catecholamines; D018847:Opioid Peptides; D011759:Pyrrolidines; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; D009538:Nicotine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; C045444:U 69593