中国药理学与毒理学杂志2026，Vol.40Issue(7)：529-534,6.DOI:10.3867/j.issn.1000-3002.2026.Z0206
神经肽S受体过表达及单核苷酸位点突变对μ阿片受体功能的影响
Effects of over-expression and mutation of neuropeptide S receptor on function of the mu opioid receptor
摘要
Abstract
OBJECTIVE To investigate the effects of overexpression of the neuropeptide S recep-tor(NPSR)and its single-nucleotide variant(N107I)on the function of the μ-opioid receptor(OPRM).METHODS HEK293T cell lines were established via lentiviral infection:one stably expressing the OPRM(OPRM),one stably co-expressing the OPRM and NPSR N107(OPRM/NPSR N107),and one stably co-expressing the OPRM and NPSR I107(OPRM/NPSR I107).The mRNA and total protein levels of OPRM and NPSR in these cells were determined by RT-qPCR and Western blotting,respec-tively.For cAMP assays,cells were acutely co-treated with morphine(0.01,0.1,1,and 10 μmol·L-1)and the adenylyl cyclase activator forskolin(1 μmol·L-1)for 30 min before levels of intracellular cyclic adenosine monophosphate(cAMP)were measured by homogeneous time-resolved fluorescence assay.For ERK phosphorylation assays,cells were acutely treated with morphine(0.1,1,and 10 μmol·L-1)for 5 min,and levels of extracellular signal-regulated kinase(ERK)phosphorylation were determined by Western blotting.RESULTS Compared with OPRM cells,intracellular cAMP levels were significantly increased by forskolin(1 μmol·L-1)in both OPRM/NPSR N107 and OPRM/NPSR I107 cells,especially OPRM/NPSR N107 cells.Intracellular cAMP levels were significantly decreased by morphine(1 and 10 μmol·L-1)in OPRM cells and In OPRM/NPSR N107 cells(0.1,1,and 10 μmol·L-1),but only signifi-cantly decreased by the high concentration of morphine(10 μmol·L-1)in OPRM/NPSR I107 cells.Compared with OPRM cells,morphine-induced ERK phosphorylation was higher in OPRM/NPSR N107 cells but lower in OPRM/NPSR I107 cells.CONCLUSION The overexpression of NPSR can enhance intracellular adenylyl cyclase activity while the NPSR N107I variant can attenuate the morphine-induced decrease in cAMP levels and ERK phosphorylation following acute morphine treatment.关键词
神经肽S受体/突变/阿片受体功能/环磷酸腺苷/细胞外信号调节蛋白激酶Key words
neuropeptide S receptor/variant/μ-opioid receptor function/cyclic adenosine mono-phosphate/extracellular signal-regulated kinase分类
医药卫生引用本文复制引用
宋晨,刘钏钏,李锦,宋睿,吴宁,李斐..神经肽S受体过表达及单核苷酸位点突变对μ阿片受体功能的影响[J].中国药理学与毒理学杂志,2026,40(7):529-534,6.基金项目
国家自然科学基金项目(81973303) National Nature Science Foundation of China(81973303) （81973303）
