Gandhi V C, Ross D H
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
Neurochem Res. 1988 Dec;13(12):1175-81. doi: 10.1007/BF00971636.
The in vivo effect of the mu agonist morphine and antagonist naloxone on [3H]nimodipine receptor binding in rat brain regions has been investigated. Morphine administration (15 mg/s.c.) for thirty minutes produced a 19% decrease in [3H]nimodipine receptor binding (Bmax 158.2 fmol to 128.9 fmol) in cortex and 29% decrease in cerebellum (65.3 fmol to 46.0 fmol). Lesser changes were observed in hippocampal and striatal regions with no changes in hypothalamus and brain stem. All effects were completely antagonized by naloxone pretreatment (1 mg/kg). The studies suggest that opiates in vivo can alter [3H]nimodipine binding to the Ca2+ channel receptor protein. These findings agree with the previously observed decreases in Ca2+ influx in nerve ending preparations and inhibition of ICa2+ following opiate treatment and suggest opiates reduce Ca2+-dependent neurotransmitter release by altering the Ca2+ channel receptor protein in an allosteric fashion.
已研究了μ阿片受体激动剂吗啡和拮抗剂纳洛酮对大鼠脑区[³H]尼莫地平受体结合的体内效应。皮下注射吗啡（15毫克）30分钟后，皮层中[³H]尼莫地平受体结合（Bmax从158.2飞摩尔降至128.9飞摩尔）下降了19%，小脑下降了29%（从65.3飞摩尔降至46.0飞摩尔）。海马和纹状体区域变化较小，下丘脑和脑干无变化。纳洛酮预处理（1毫克/千克）可完全拮抗所有效应。这些研究表明，体内阿片类药物可改变[³H]尼莫地平与Ca²⁺通道受体蛋白的结合。这些发现与先前观察到的神经末梢制剂中Ca²⁺内流减少以及阿片类药物治疗后ICa²⁺受到抑制一致，并表明阿片类药物通过变构方式改变Ca²⁺通道受体蛋白，从而减少Ca²⁺依赖性神经递质释放。
