title: Lack of autoreceptor-mediated inhibitory control of dopamine release in striatal synaptosomes of D2 receptor-deficient mice.
abstract: Mouse purified striatal synaptosomes were used to study the release of newly synthesised [3H]-dopamine ([3H]-DA) or of previously taken up [3H]-DA. Quinpirole (QP, 10 microM), a D2/D3 dopaminergic agonist, was found to reduce the release of newly synthesised [3H]-DA with a larger amplitude when 4-aminopyridine (100 microM) instead than veratridine (1 microM) or potassium (25 mM) was used to evoke DA release. Among the different D2/D3 dopaminergic agonists tested R(-)-propylnorapomorphine (NPA) and quinpirole were the most potent. These compounds reduced, in a concentration-dependent manner, the 4-aminopyridine-evoked release of [3H]-DA previously taken up by synaptosomes (50% maximal inhibition). In contrast, the D3 agonist PD-128,907 had little effect even when used at 100 nM. The QP (100 nM)-induced response was completely antagonised by sulpiride (1 microM). Strikingly, the NPA (100 nM) and PD-128,907 (100 nM)-evoked responses were completely suppressed in D2 receptor-deficient mice. This data strongly suggest that only D2 but not D3 receptors are involved in the autoreceptor-mediated inhibition of the evoked release of [3H]-DA. Interestingly, while amphetamine-induced release of [3H]-DA was not modified, a slight reduction of [3H]-DA efflux induced by the dopamine (DA) uptake inhibitor cocaine was observed in D2 receptor-deficient mice.
authors.affiliation: Chaire de Neuropharmacologie (INSERM U.114), Paris Cedex 75231, France.
authors.forename: M
authors.initials: M
authors.lastname: L'hirondel
authors.forename: A
authors.initials: A
authors.lastname: Chéramy
authors.forename: G
authors.initials: G
authors.lastname: Godeheu
authors.forename: F
authors.initials: F
authors.lastname: Artaud
authors.forename: A
authors.initials: A
authors.lastname: Saiardi
authors.forename: E
authors.initials: E
authors.lastname: Borrelli
authors.forename: J
authors.initials: J
authors.lastname: Glowinski
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D017660:Autoreceptors / Q000819:agonists / Q000502:physiology*; D001578:Benzopyrans / Q000494:pharmacology; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology*; D010078:Oxazines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000737:chemistry; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D013574:Synaptosomes / Q000737:chemistry / Q000378:metabolism; D014316:Tritium
chemical_list: C077797:2-(N-phenylethyl-N-propyl)amino-5-hydroxytetralin fluorescein; D017660:Autoreceptors; D001578:Benzopyrans; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D005452:Fluoresceins; D010078:Oxazines; D017448:Receptors, Dopamine D2; D014316:Tritium; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D019257:Quinpirole; C009074:N-n-propylnorapomorphine; D011189:Potassium Chloride; D015761:4-Aminopyridine; D000661:Amphetamine; C066444:cocaethylene; D003042:Cocaine; D001058:Apomorphine; D004298:Dopamine