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• W1977963554 abstract "The effect of muscarinic agonists on the spontaneous release of [3H]GABA was investigated in vitro on rat substantia nigra slices. Acetylcholine (5 × 10−5M) in the presence of eserine (5 × 10−5M) induced a 12.3% increase of the spontaneous release of [3H]GABA. Similarly, carbachol (5 × 10−4M) enhanced by 9% the release of [3H]GABA. This effect was Ca2+-dependent, it was abolished in the presence of 0.4 mM Ca2+ and enhanced from 9 to 17% when Ca2+-concentration of the superfusion medium was increased from 1.3 to 2.4 mM. The carbachol effect was mediated by muscarinic receptors since it was abolished by atropine (2 × 10−6M). The pharmacologically M2 muscarinic receptor subtypes seems to be involved as the carbachol-induced effect was abolished by AF-DX384MS (10−6 M), an M2 antagonist and was only partially reversed by pirenzepine (10−5 and 10−4 M), an M1 antagonist which at these doses also block the M2 receptors. The absence of effect of SCH23390 (10−6 M) a D1 antagonist as well as the lack of effect of CNQX (10−5 M) and dizocilpine maleate (10−6 M), two glutamate antagonists, on the carbachol-induced effect indicated that neither dopamine (through D1 receptors) nor glutamate (through ionotropic receptors) were involved in the response. In addition, the persistence of the carbachol-induced effect in the presence of tetrodotoxin (2 × 10−7M) suggests a direct muscarinic-medited modulation of [3H]GABA. The localization of muscarinic receptors on striatonigral fibres was confirmed by autoradiographic studies showing a decrease of [3H]pirenzepine binding in the substantia nigra after a unilateral striatal lesion induced by kainic acid injection. This latter result provides evidence of the presence of M1 receptors on striatonigral terminals as the concentration of [3H]pirenzepine used (10 nM) is M1-selective. These results indicate a cholinergic modulation of GABA release in the rat substantia nigra mediated by muscarinic receptors localized on striatonigral terminals. The involvement of the m4 muscarinic receptor subtype that have a M1/M2 pharmacology is discussed." @default.
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• W1977963554 date "1994-12-01" @default.
• W1977963554 modified "2023-10-17" @default.
• W1977963554 title "Muscarinic receptor stimulation increases the spontaneous [3H]GABA release in the rat substantia nigra through muscarinic receptors localized on striatonigral terminals" @default.
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• W1977963554 doi "https://doi.org/10.1016/0306-4522(94)90567-3" @default.
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