Christie M J
Department of Pharmacology, University of Sydney, N.S.W., Australia.
Prog Brain Res. 1991;88:197-205. doi: 10.1016/s0079-6123(08)63809-1.
The locus coeruleus (LC) has provided a useful model for pioneering studies of the mechanisms underlying the acute and chronic actions of opioid drugs. Acutely, opioids inhibit the electrical activity of single neurons in the rat and guinea pig LC. Inhibition is due to a membrane hyperpolarisation. In these cells, opioids act on mu-receptors to increase the opening of inwardly rectifying potassium channels, thus leading to hyperpolarisation. The mu-receptors are coupled to potassium channels via G-proteins which are sensitive to inactivation by pertussis toxin. This coupling process is quite direct, in that it does not involve freely diffusible intracellular second messengers. Agonists specific for other receptors, such as alpha 2- and somatostatin-receptors, are capable of opening the same population of potassium channels on LC neurons. Following chronic treatment of animals with morphine, a specific deficit develops in the ability of mu-receptors to open potassium channels, producing reduced sensitivity of LC neurons to inhibition by opioids.
蓝斑核（LC）为开展阿片类药物急性和慢性作用机制的开拓性研究提供了一个有用的模型。急性给药时，阿片类药物会抑制大鼠和豚鼠蓝斑核中单个神经元的电活动。抑制作用是由于膜超极化所致。在这些细胞中，阿片类药物作用于μ受体，增加内向整流钾通道的开放，从而导致超极化。μ受体通过对百日咳毒素失活敏感的G蛋白与钾通道偶联。这种偶联过程相当直接，因为它不涉及可自由扩散的细胞内第二信使。对其他受体特异的激动剂，如α2受体和生长抑素受体的激动剂，能够打开蓝斑核神经元上相同的钾通道群。用吗啡对动物进行长期治疗后，μ受体打开钾通道的能力出现特定缺陷，导致蓝斑核神经元对阿片类药物抑制作用的敏感性降低。
