Di Marzo V, Vial D, Sokoloff P, Schwartz J C, Piomelli D
Unité de Neurobiologie et Pharmacologie de I'INSERM, Paris, France.
J Neurosci. 1993 Nov;13(11):4846-53. doi: 10.1523/JNEUROSCI.13-11-04846.1993.
Evidence indicates that a single membrane receptor subtype may be responsible for the generation of multiple intracellular signals, but mechanisms allowing for the selection of a specific effector pathway have not yet been documented. In neurons and other cells, the stimulation of dopamine D2 receptors produces, via G-protein activation, a spectrum of intracellular responses including inhibition of adenylyl cyclase activity, modulation of K+ currents, and potentiation of Ca(2+)-evoked arachidonic acid (AA) release. In this study, we report that, in Chinese hamster ovary cells, stimulation of protein kinase C (PKC) directs the preferential coupling of transfected D2 receptors from inhibition of adenylyl cyclase to potentiation of AA release, two responses mediated by Gi. The switch between these two signaling systems is accompanied by marked changes in their GTP sensitivities, indicating that it may result from the phosphorylation of component(s) of the receptor-Gi-protein complex. Brain PKC activity is enhanced by neurotransmitters and by neuronal depolarization. Thus, the ability of this protein kinase to remodel signaling pathways at the D2 receptor may regulate these Gi-mediated responses in an activity-dependent manner, and represent a novel form of synaptic plasticity.
有证据表明，单一的膜受体亚型可能负责多种细胞内信号的产生，但允许选择特定效应器途径的机制尚未得到证实。在神经元和其他细胞中，多巴胺D2受体的刺激通过G蛋白激活产生一系列细胞内反应，包括抑制腺苷酸环化酶活性、调节钾离子电流以及增强钙离子诱发的花生四烯酸（AA）释放。在本研究中，我们报告，在中国仓鼠卵巢细胞中，蛋白激酶C（PKC）的刺激引导转染的D2受体从抑制腺苷酸环化酶到增强AA释放的优先偶联，这两种反应均由Gi介导。这两种信号系统之间的转换伴随着它们对GTP敏感性的显著变化，表明这可能是由受体-Gi蛋白复合物成分的磷酸化导致的。神经递质和神经元去极化可增强脑PKC活性。因此，这种蛋白激酶在D2受体处重塑信号通路的能力可能以活动依赖的方式调节这些Gi介导的反应，并代表一种新型的突触可塑性。
