Yu V C, Sadée W
Department of Pharmacy and Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco.
J Pharmacol Exp Ther. 1988 Apr;245(1):350-5.
Upon differentiation with retinoic acid of the human neuroblastoma cells SH-SY5Y into mature neurons, opioid drugs become highly effective in suppressing prostaglandin E1 (50% inhibition)- and forskolin (70% inhibition)-stimulated adenylate cyclase activity, which was assessed by measuring cyclic AMP accumulation in intact cells. Whereas the SH-SY5Y cells carry both mu and delta receptors in a ratio of mu/delta approximately equal to 5/1, the response is predominantly mediated by the mu receptor. Morphine acts as a strong agonist with an EC50 of 50 to 100 nM which falls into the therapeutic range expected for narcotic analgesic effects mediated by the mu receptor. Narcotic analgesic drugs with only partial agonism fail to evoke full response, which suggests that this cell model could provide a rapid screening assay for narcotic analgesic efficacy. Continued exposure of the cells to morphine resulted in partial tolerance within 12 hr with a 4-fold shift of morphine's EC50 to higher concentrations, whereas longer morphine exposure did not cause any further shift. Thus, the differentiated SH-SY5Y cells provide a suitable system for studying the molecular mechanisms of the narcotic analgesics.
在人神经母细胞瘤细胞SH-SY5Y用视黄酸诱导分化为成熟神经元后，阿片类药物在抑制前列腺素E1（50%抑制率）和福斯可林（70%抑制率）刺激的腺苷酸环化酶活性方面变得非常有效，这是通过测量完整细胞中环磷酸腺苷的积累来评估的。虽然SH-SY5Y细胞同时携带μ和δ受体，其μ/δ比例约为5/1，但该反应主要由μ受体介导。吗啡作为一种强效激动剂，其半数有效浓度（EC50）为50至100 nM，属于由μ受体介导的麻醉性镇痛作用预期的治疗范围。仅具有部分激动作用的麻醉性镇痛药无法引发完全反应，这表明该细胞模型可为麻醉性镇痛效果提供一种快速筛选测定法。细胞持续暴露于吗啡会在12小时内产生部分耐受性，吗啡的EC50向更高浓度有4倍的偏移，而更长时间的吗啡暴露并未导致进一步的偏移。因此，分化后的SH-SY5Y细胞为研究麻醉性镇痛药的分子机制提供了一个合适的系统。
