Almela Pilar, Cerezo Manuela, Milanés M Victoria, Laorden M Luisa
Equip of Cellular and Molecular Pharmacology, University School of Medicine, Murcia, Spain.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Feb;372(5):374-82. doi: 10.1007/s00210-006-0032-y. Epub 2006 Feb 11.
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.
我们之前证明，通过去甲肾上腺素（NA）周转率和Fos表达评估，吗啡戒断通过激活支配左、右心室的去甲肾上腺素能通路诱导心脏活动亢进。本研究旨在通过评估蛋白激酶C（PKC）的药理学抑制是否会减弱吗啡戒断诱导的Fos表达以及左、右心室中酪氨酸羟化酶（TH）免疫反应性水平和NA周转率的变化，来研究PKC在此过程中的作用。在第8天通过注射纳洛酮诱导吗啡依赖。吗啡戒断诱导Fos表达，并增加右心室和左心室中的TH水平及NA周转率。注入选择性PKC抑制剂钙泊三醇，并未改变吗啡戒断诱导的NA周转率和TH水平的升高。然而，该抑制剂使吗啡戒断诱导的Fos表达减少。本研究结果为吗啡戒断诱导心脏中Fos表达上调的机制提供了新信息，并表明在心脏水平的吗啡戒断过程中，TH不是PKC的作用靶点。
