Kaneko S, Nakamura S, Adachi K, Akaike A, Satoh M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Brain Res Mol Brain Res. 1994 Dec;27(2):258-64. doi: 10.1016/0169-328x(94)90008-6.
The intracellular metabotropic pathway, following kappa opioid receptor activation, was investigated in the Xenopus oocyte translation system. When oocytes were injected with cRNA for kappa opioid receptor cDNA, U50488H rarely evoked phospholipase C-mediated, oscillatory Cl- current responses. However, after the oocytes were incubated with staurosporine, both the occurrence and the amplitude of U50488H-evoked responses were increased. The U50488H-evoked response was antagonized by naloxone and inhibited by pretreatment of the oocytes with pertussis toxin. When oocytes were coinjected with RNAs encoding kappa opioid receptor and cystic fibrosis transmembrane conductance regulator (CFTR), treatment of the oocytes with forskolin and 3-isobutyl-1-methylxanthine (IBMX) evoked a smooth-shaped Cl- current flowing through the CFTR channels. The forskolin/IBMX-evoked response was never inhibited but was greatly potentiated in the presence of U50488H, indicating stimulation of adenylyl cyclase by U50488H. This U50488H-induced potentiation of CFTR channel opening was antagonized by naloxone and inhibited by pretreatment with pertussis toxin. These results suggest that kappa opioid receptors mobilize intracellular Ca2+ and stimulate cyclic AMP production by coupling positively to both phospholipase C and adenylyl cyclase via pertussis toxin-sensitive GTP-binding proteins in the oocytes.
在非洲爪蟾卵母细胞翻译系统中，对κ阿片受体激活后的细胞内代谢型信号通路进行了研究。当向卵母细胞注射κ阿片受体cDNA的cRNA时，U50488H很少诱发磷脂酶C介导的振荡性Cl-电流反应。然而，在卵母细胞与星形孢菌素孵育后，U50488H诱发反应的发生率和幅度均增加。U50488H诱发的反应可被纳洛酮拮抗，并被用百日咳毒素预处理卵母细胞所抑制。当向卵母细胞共注射编码κ阿片受体和囊性纤维化跨膜电导调节因子（CFTR）的RNA时，用福斯可林和3-异丁基-1-甲基黄嘌呤（IBMX）处理卵母细胞可诱发流经CFTR通道的平滑型Cl-电流。福斯可林/IBMX诱发的反应从未被抑制，但在存在U50488H的情况下会大大增强，表明U50488H可刺激腺苷酸环化酶。这种U50488H诱导的CFTR通道开放增强作用可被纳洛酮拮抗，并被用百日咳毒素预处理所抑制。这些结果表明，κ阿片受体通过卵母细胞中对百日咳毒素敏感的GTP结合蛋白与磷脂酶C和腺苷酸环化酶正性偶联，从而动员细胞内Ca2+并刺激环磷酸腺苷的产生。
