Role of PKC in regulation of Fos and TH expression after naloxone induced morphine withdrawal in the heart.
We previously demonstrated that morphine withdrawal induced hyperactivity of the heart by activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline (NA) turnover and Fos expression. The present study was designed to investigate the role of protein kinase C (PKC) in this process, by estimating whether pharmacological inhibition of PKC would attenuate morphine withdrawal induced Fos expression and changes in tyrosine hydroxylase (TH) immunoreactivity levels and NA turnover in the left and right ventricle. Dependence on morphine was induced on day 8 by an injection of naloxone. Morphine withdrawal induced Fos expression and increased TH levels and NA turnover in the right and left ventricle. Infusion of calphostin C, a selective PKC inhibitor, did not modify the morphine withdrawal-induced increase in NA turnover and TH levels. However, this inhibitor produced a reduction in the morphine withdrawal-induced Fos expression. The results of the present study provide new information on the mechanisms that underlie morphine withdrawal-induced up-regulation of Fos expression in the heart and suggest that TH is not a target of PKC during morphine withdrawal at heart levels.
Equip of Cellular and Molecular Pharmacology, University School of Medicine, Murcia, Spain.
Pilar
P
Almela
Manuela
M
Cerezo
M Victoria
MV
Milanés
M Luisa
ML
Laorden
D000818:Animals; D006352:Heart Ventricles; D008297:Male; D009020:Morphine / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D009206:Myocardium / Q000378:metabolism*; D009270:Naloxone; D009281:Naphthalenes / Q000494:pharmacology; D009292:Narcotic Antagonists; D009638:Norepinephrine / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D009281:Naphthalenes; D009292:Narcotic Antagonists; D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D009270:Naloxone; D009020:Morphine; D014446:Tyrosine 3-Monooxygenase; D011493:Protein Kinase C; C058819:calphostin C; D009638:Norepinephrine