OPIOID-PEPTIDES ACTIVATE PHOSPHOLIPASE-D AND PROTEIN KINASE-C-EPSILON IN CHICKEN-EMBRYO NEURON CULTURES
OPIOID-PEPTIDES ACTIVATE PHOSPHOLIPASE-D AND PROTEIN KINASE-C-EPSILON IN CHICKEN-EMBRYO NEURON CULTURES
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DOI：
10.1073/pnas.90.7.2915
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发表时间：
1993-04-01
影响因子：
11.1
通讯作者：
DAWSON, G
中科院分区：
文献类型：
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作者：
MANGOURA, D;DAWSON, G
μ阿片肽形态肽刺激Ca 2+非依赖性蛋白激酶C（PKC-epsilon），该蛋白激酶C在胚胎第6天鸡端脑和衍生神经元培养物中表达。这种激活被认为是2倍的活性和水平的胞浆PKC-β的增加，并作为一个短暂的增加，膜相关的PKC-β后morphiceptin治疗。吗啡肽没有激活磷脂酶C介导的磷脂酰肌醇水解，但短暂激活（2至3倍）磷脂酶D（PLD），如测量的磷脂酰乙醇形成的神经元培养物来自胚胎第6天或第7天的大脑半球。这种PLD激活可以为PKC-β的激活提供二酰基甘油的替代来源，并且是纳洛酮可逆的，并且至少部分地被酪氨酸激酶抑制剂除莠霉素A阻断。此外，佛波醇12-肉豆蔻酸酯13-乙酸酯刺激PLD和PKC-β的活动在更大程度上比阿片类药物。除莠霉素可阻断佛波酯和胰岛素对PLD的刺激作用。吗啡肽（以纳洛酮可逆的方式）和佛波酯增加了完整细胞中类似胞质蛋白的磷酸化，证明了阿片类药物对PKC β激活的功能作用。这是阿片受体与酪氨酸激酶、PLD和PKC-ERK激活瞬时偶联的证据，并暗示在脑形态发生期间与神经元细胞生长偶联。
The mu-opioid peptide morphiceptin stimulated a Ca2+-independent protein kinase C (PKC-epsilon) that is expressed both in embryonic day 6 chicken telencephalon and in derived neuronal cultures. This activation was seen as a 2-fold increase in the activity and level of cytosolic PKC-epsilon and as a transient increase in membrane-associated PKC-epsilon following morphiceptin treatment. Morphiceptin did not activate phospholipase C-mediated phosphatidylinositol hydrolysis but did transiently activate (2- to 3-fold) phospholipase D (PLD), as measured by phosphatidylethanol formation in neuron cultures derived from embryonic day 6 or day 7 cerebral hemispheres. This PLD activation could provide an alternative source of diacylglycerol for the activation of PKC-epsilon and was naloxone-reversible and at least partially blocked by the tyrosine kinase inhibitor herbimycin A. Addition of phorbol 12-myristate 13-acetate stimulated both PLD and PKC-epsilon activities to a greater extent than opioids. The phorbol ester and insulin stimulation of PLD was also blocked by herbimycin. Both morphiceptin (in a naloxone-reversible manner) and phorbol ester increased phosphorylation of similar cytosolic proteins in intact cells, demonstrating a functional role for the PKC-epsilon activation by opioids. This is evidence that opioid receptors are transiently coupled to tyrosine kinase, PLD and PKC-epsilon activation and, by implication, to neuronal cell growth during brain morphogenesis.