Llorens-Cortes C, Zini S, Gros C, Schwartz J C
Unité de Neurobiologie et Pharmacologie (U. 109) de l'INSERM, Centre Paul Broca, Paris, France.
J Neurochem. 1991 Apr;56(4):1368-75. doi: 10.1111/j.1471-4159.1991.tb11434.x.
The effects of dopamine receptor stimulation on enkephalin release were evaluated in vitro and in vivo by measuring the changes in the levels of [Met5]enkephalin (YGGFM) and Tyr-Gly-Gly (YGG), a characteristic extracellular enkephalin metabolite produced under the action of enkephalinase. In rat striatal slices, D1-receptor agonists or antagonists did not modify enkephalin release. By contrast, D2-receptor agonists enhanced the potassium-induced release of YGGFM and YGG without affecting spontaneous release from nondepolarized slices. This response was prevented by the D2-receptor antagonists haloperidol and RIV 2093, the latter compound being more potent, which suggested the involvement of a putative D2-receptor subtype. Acute administration of apomorphine or selective D2-receptor agonists, but not that of a D1-receptor agonist, enhanced the steady-state level of YGG without affecting the YGGFM level in rat striatum. The effect was blocked selectively by D2-receptor antagonists which, administered alone, had no effect. These observations indicate that D2-receptor stimulation in vitro or in vivo facilitates enkephalin release from striatal neurons, but that endogenous dopamine does not exert any tonic influence upon the opioid peptide neuron activity under basal conditions. However, chronic administration of haloperidol resulted in increases in striatal YGGFM and YGG, an effect presumably reflecting a long-term adaptive process.
通过测量[Met5]脑啡肽（YGGFM）和Tyr-Gly-Gly（YGG）水平的变化，在体外和体内评估多巴胺受体刺激对脑啡肽释放的影响，YGG是在脑啡肽酶作用下产生的一种典型的细胞外脑啡肽代谢产物。在大鼠纹状体切片中，D1受体激动剂或拮抗剂不会改变脑啡肽的释放。相比之下，D2受体激动剂可增强钾诱导的YGGFM和YGG释放，而不影响非去极化切片的自发释放。D2受体拮抗剂氟哌啶醇和RIV 2093可阻止这种反应，后一种化合物效力更强，这表明可能涉及一种假定的D2受体亚型。急性给予阿扑吗啡或选择性D2受体激动剂可提高大鼠纹状体中YGG的稳态水平，但D1受体激动剂则无此作用，且不影响YGGFM水平。该效应被D2受体拮抗剂选择性阻断，单独给予这些拮抗剂则无作用。这些观察结果表明，体外或体内的D2受体刺激可促进纹状体神经元释放脑啡肽，但内源性多巴胺在基础条件下对阿片肽神经元活性没有任何紧张性影响。然而，长期给予氟哌啶醇会导致纹状体YGGFM和YGG增加，这一效应可能反映了一种长期的适应性过程。
