Clouet D H, Williams N, Yonehara N
Life Sci. 1983;33 Suppl 1:727-30. doi: 10.1016/0024-3205(83)90605-7.
The effect of several opioids: methadone, etorphine, beta-endorphin and D-ala2met enkephalin on Ca++/calmodulin stimulation of enzyme activities either in pure solution (cyclic nucleotide phosphodiesterase) or in striatal membranes (protein kinases in synaptic membranes) were compared to see if a direct opioid/calmodulin interaction could eliminate the stimulation of enzyme activity as part of the mechanism by which opioids alter ion flow and neurotransmitter release. In other experiments, in which endogenous phosphorylation of proteins in striatal synaptic membranes was altered by opioid treatments, the possibility of restoring protein kinase activity to normal levels in the membrane preparation by supplementation with calmodulin at optimal Ca++ concentration was examined. Some opioids (methadone and D-ala2met enkephalin) did not inhibit calmodulin-stimulated phosphodiesterase, which suggests that they were not able to bind to calmodulin. In addition, it was not possible to restore decreases in protein kinase activity to normal levels by adding calmodulin to the assay in the presence of optimal Ca++. We conclude that a direct binding of opioids to calmodulin is not a general mechanism of opioid action, although the binding may participate in the action of some neuropeptides, including beta-endorphin.
美沙酮、埃托啡、β-内啡肽和D-丙氨酸2-甲硫氨酸脑啡肽对纯溶液（环核苷酸磷酸二酯酶）或纹状体膜（突触膜中的蛋白激酶）中Ca++/钙调蛋白刺激的酶活性的影响，以确定阿片类药物与钙调蛋白的直接相互作用是否可以消除酶活性的刺激，作为阿片类药物改变离子流动和神经递质释放机制的一部分。在其他实验中，通过阿片类药物处理改变纹状体突触膜中蛋白质的内源性磷酸化，研究了在最佳Ca++浓度下通过补充钙调蛋白将膜制剂中的蛋白激酶活性恢复到正常水平的可能性。一些阿片类药物（美沙酮和D-丙氨酸2-甲硫氨酸脑啡肽）不抑制钙调蛋白刺激的磷酸二酯酶，这表明它们不能与钙调蛋白结合。此外，在存在最佳Ca++的情况下，通过向测定中添加钙调蛋白，不可能将蛋白激酶活性的降低恢复到正常水平。我们得出结论，阿片类药物与钙调蛋白的直接结合不是阿片类药物作用的普遍机制，尽管这种结合可能参与某些神经肽（包括β-内啡肽）的作用。
