Ethanol alters opioid regulation of Ca(2+) influx through L-type Ca(2+) channels in PC12 cells.
Ethanol alters opioid regulation of Ca(2+) influx through L-type Ca(2+) channels in PC12 cells.
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DOI：
10.1111/j.1530-0277.2011.01631.x
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Terenius L
中科院分区：
文献类型：
--
作者：
Gruol DL;Nelson TE;Hao C;Michael S;Vukojevic V;Ming Y;Terenius L
行为和突触水平的研究表明，乙醇对中枢神经系统的影响可能涉及阿片信号系统。这些相互作用可能会改变一个共同的下游目标的功能。在这项研究中，我们研究了Ca 2+通道功能作为乙醇和μ或κ阿片受体信号之间相互作用的潜在下游靶点。这些研究是在模型系统中进行的，未分化的PC 12细胞转染μ或κ阿片受体。PC 12细胞表达L-型钙通道，该通道可被K+去极化激活。Ca 2+成像用于测量K+去极化过程中的相对Ca 2+通量以及阿片类药物和乙醇对Ca 2+通量的调节。乙醇、μ受体激活和κ受体激活均降低了由K+去极化产生的Ca 2+信号的幅度。用乙醇预处理或用乙醇和μ或κ受体激动剂联合处理引起Ca 2+信号幅度的降低，其与单独使用单个药物观察到的幅度相当或更小，表明药物在下游靶点（或多个靶点）的相互作用限制了通过L型Ca 2+通道的Ca 2+通量的调节。这些研究为乙醇通过与阿片信号相互作用调节突触传递和行为的细胞机制提供了证据。
Studies at the behavioral and synaptic level show that effects of ethanol on the central nervous system can involve the opioid signaling system. These interactions may alter the function of a common downstream target. In this study, we examined Ca2+ channel function as a potential downstream target of interactions between ethanol and mu or kappa opioid receptor signaling. The studies were carried out in a model system, undifferentiated PC12 cells transfected with mu or kappa opioid receptors. The PC12 cells express L-type Ca2+ channels, which were activated by K+ depolarization. Ca2+ imaging was used to measure relative Ca2+ flux during K+ depolarization and the modulation of Ca2+ flux by opioids and ethanol. Ethanol, mu receptor activation and kappa receptor activation all reduced the amplitude of the Ca2+ signal produced by K+ depolarization. Pretreatment with ethanol or combined treatment with ethanol and mu or kappa receptor agonists caused a reduction in the amplitude of the Ca2+ signal that was comparable to or smaller than that observed for the individual drugs alone, indicating an interaction by the drugs at a downstream target (or targets) that limited the modulation of Ca2+ flux through L-type Ca2+ channels. These studies provide evidence for a cellular mechanism that could play an important role in ethanol regulation of synaptic transmission and behavior through interactions with the opioid signaling.
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影响因子：
3.4
作者：
Albillos, A;Carbone, E;Pollo, A
通讯作者：
Pollo, A
影响因子：
4.5
作者：
Carbone, E;Carabelli, V;Giusta, L
通讯作者：
Giusta, L
影响因子：
2.9
作者：
Kitamura, G;Ohta, T;Ito, S
通讯作者：
Ito, S
影响因子：
2.8
作者：
HOEK, JB;RUBIN, E
通讯作者：
RUBIN, E
影响因子：
25
作者：
Aryal, Prafulla;Dvir, Hay;Choe, Senyon;Slesinger, Paul A.
通讯作者：
Slesinger, Paul A.