Piomelli D, Pilon C, Giros B, Sokoloff P, Martres M P, Schwartz J C
Unité de Neurobiologie et Pharmacologie (U. 109) de I'INSERM, Centre Paul Broca, Paris, France.
Nature. 1991 Sep 12;353(6340):164-7. doi: 10.1038/353164a0.
Understanding the actions of the neurotransmitter dopamine in the brain is important in view of its roles in neuropsychiatric illnesses. Dopamine D1 receptors, which stimulate both adenylyl cyclase and phospholipase C, and D2 receptors, which inhibit them, can nevertheless act synergistically to produce many electrophysiological and behavioral responses. Because this functional synergism can occur at the level of single neurons, another, as yet unidentified, signalling pathway activated by dopamine has been hypothesized. We report here that in Chinese hamster ovary (CHO) cells transfected with the D2 receptor complementary DNA, D2 agonists potently enhanced arachidonic acid release, provided that such release has been initiated by stimulating constitutive purinergic receptors or by increasing intracellular Ca2+. In CHO cells expressed D1 receptors, D1 agonists exert no such effect. When D1 and D2 receptors are coexpressed, however, activation of both subtypes results in a marked synergistic potentiation of arachidonic acid release. The numerous actions of arachidonic acid and its metabolites in neuronal signal transduction suggest that facilitation of its release may be implicated in dopaminergic responses, such as feedback inhibition mediated by D2 autoreceptors, and may constitute a molecular basis for D1/D2 receptor synergism.
鉴于神经递质多巴胺在神经精神疾病中的作用，了解其在大脑中的作用非常重要。多巴胺D1受体可刺激腺苷酸环化酶和磷脂酶C，而D2受体则抑制它们，但它们仍可协同作用产生许多电生理和行为反应。由于这种功能协同作用可在单个神经元水平上发生，因此有人推测多巴胺还激活了另一条尚未确定的信号通路。我们在此报告，在中国仓鼠卵巢（CHO）细胞中转入D2受体互补DNA后，只要通过刺激组成型嘌呤能受体或增加细胞内Ca2+引发花生四烯酸释放，D2激动剂就能有效增强花生四烯酸的释放。在表达D1受体的CHO细胞中，D1激动剂则没有这种作用。然而，当D1和D2受体共表达时，两种亚型的激活会导致花生四烯酸释放显著协同增强。花生四烯酸及其代谢产物在神经元信号转导中的众多作用表明，其释放的促进可能与多巴胺能反应有关，如D2自身受体介导的反馈抑制，并且可能构成D1/D2受体协同作用的分子基础。
