Dopaminergic regulation of enkephalin release.
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.
Llorens-Cortes
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C
Unité de Neurobiologie et Pharmacologie (U. 109) de l'INSERM, Centre Paul Broca, Paris, France.
Zini
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S
Gros
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C
Schwartz
J C
JC
D000818:Animals; D001921:Brain / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009842:Oligopeptides / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D015259:Dopamine Agents; D004745:Enkephalins; D009842:Oligopeptides; C044757:tyrosyl-glycyl-glycine; D004744:Enkephalin, Methionine; D006220:Haloperidol; D011188:Potassium; D004298:Dopamine