Harder D R, Madden J A
Eur J Pharmacol. 1984 Jul 20;102(3-4):411-6. doi: 10.1016/0014-2999(84)90560-0.
To determine some of the cellular mechanisms of opiate receptor stimulation in cat middle cerebral arterial muscle, intracellular electrical measurements and force development were monitored before and after addition of morphine. Addition of morphine resulted in a dose-dependent hyperpolarization of the muscle cells in the middle cerebral artery with a concomitant relaxation, indicating a high degree of electromechanical coupling in this preparation. The curve relating membrane potential vs. morphine was shifted to the right and downward by naloxone, demonstrating competitive inhibition at receptor sites. When middle cerebral arteries were studied from animals which had been injected with morphine prior to sacrifice, a significant hyperpolarization of the membrane was recorded when studied in an organ bath. This hyperpolarization was abolished if the animal had been pretreated with naloxone prior to morphine injection, suggesting that morphine may act in vivo as we have observed it to act in vitro. Morphine-induced hyperpolarization could be blocked in the organ bath when potassium conductance (gk) was inhibited. Similarly, the reduction in the slope of the voltage/current curve induced by morphine was blocked by agents which reduced gk. These data suggest the presence of opiate receptors on cat cerebral artery and suggest that morphine relaxes these vessels through a mechanism involving increased gk. These findings suggest a role for opiate-mediated systems in cerebral vascular control.
为了确定猫大脑中动脉肌肉中阿片受体刺激的一些细胞机制，在添加吗啡前后监测细胞内电测量和力的产生。添加吗啡导致大脑中动脉肌肉细胞出现剂量依赖性超极化，并伴有舒张，表明该制剂中存在高度的机电耦合。纳洛酮使膜电位与吗啡关系曲线向右下方移动，证明在受体部位存在竞争性抑制。当研究处死前注射过吗啡的动物的大脑中动脉时，在器官浴中进行研究时记录到膜的显著超极化。如果动物在注射吗啡前用纳洛酮预处理，这种超极化就会消失，这表明吗啡在体内的作用方式与我们在体外观察到的一致。当钾电导（gk）被抑制时，器官浴中吗啡诱导的超极化可被阻断。同样，吗啡诱导的电压/电流曲线斜率降低也被降低gk的药物所阻断。这些数据表明猫脑动脉上存在阿片受体，并表明吗啡通过涉及gk增加的机制使这些血管舒张。这些发现提示阿片介导系统在脑血管控制中发挥作用。
