McFadzean I
Parke-Davis Research Unit, Addenbrooke's Hospital, Cambridge, U.K.
Neuropeptides. 1988 May-Jun;11(4):173-80. doi: 10.1016/0143-4179(88)90072-8.
Recent experiments using intracellular recording techniques in vitro have revealed that common ionic mechanisms may explain the actions of opioid drugs. Evidence is now available from studies on guinea pig gut myenteric and submucous plexi, from preparations of spinal cord and dorsal root ganglia, from brain slices including the locus coeruleus and from neuroblastoma/glioma hybrid cells. The concensus is that mu opioid receptors activate an outward potassium conductance, possibly by way of adenylate cyclase. Activation of the receptor increases the membrane permeability to potassium ions and thus produces a membrane hyperpolarisation and conductance increase, plus an indirect inhibition of calcium entry during the action potential. Kappa opioids appear to inhibit directly the entry of calcium through voltage-dependent calcium channels, although to date there is no conclusive evidence that this mechanism of action can be extended to neurones of the central nervous system. The mechanism of action of delta opioids has only recently been investigated and initial evidence suggests they increase a potassium conductance similar to that increased by mu opioids. However, work in neuroblastoma x glioma hybrid cells has suggested that in these cells at least, receptor activation depress a component of voltage-dependent calcium current. The link between the receptor and the calcium channel involves a G-protein, Go.
近期在体外使用细胞内记录技术开展的实验表明，常见的离子机制或许可以解释阿片类药物的作用。目前，在豚鼠肠道肌间神经丛和黏膜下神经丛、脊髓和背根神经节标本、包括蓝斑在内的脑切片以及神经母细胞瘤/胶质瘤杂交细胞的研究中都能找到相关证据。目前的共识是，μ阿片受体可能通过腺苷酸环化酶激活外向钾电导。该受体的激活会增加细胞膜对钾离子的通透性，从而产生膜超极化和电导增加的现象，同时在动作电位期间间接抑制钙离子内流。κ阿片类药物似乎直接抑制通过电压依赖性钙通道的钙离子内流，尽管迄今为止尚无确凿证据表明这种作用机制可推广至中枢神经系统的神经元。δ阿片类药物的作用机制直到最近才得到研究，初步证据表明它们增加的钾电导与μ阿片类药物增加的类似。然而，在神经母细胞瘤x胶质瘤杂交细胞中的研究表明，至少在这些细胞中，受体激活会抑制电压依赖性钙电流的一个组成部分。受体与钙通道之间的联系涉及一种G蛋白，即Go。
