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• W2023391749 abstract "The functional role of presynaptic release-regulating metabotropic glutamate type 7 (mGlu7) receptors in hippocampal GABAergic terminals was investigated. Mouse hippocampal synaptosomes were preloaded with [3H]D-γ-aminobutyric acid ([3H]GABA) and then exposed in superfusion to 12 mM KCl. The K+-evoked [3H]GABA release was inhibited by the mGlu7 allosteric agonist N,N′-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082, 0.001–10 μM), as well as by the group III mGlu receptor agonist l-(+)-2-amino-4-phosphonobutyric acid [(l)-AP4, 0.01–1 mM]. The mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine [(S)-3,4-DCPG, 10–100 nM] was ineffective. AMN082 and (l)-AP4-induced effects were recovered by the mGlu7 negative allosteric modulator (NAM) 6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridin-4(5H)-one hydrochloride (MMPIP). AMN082 also inhibited in a MMPIP-sensitive manner the K+-evoked release of endogenous GABA. AMN082 and the adenylyl cyclase (AC) inhibitor MDL-12,330A reduced [3H]GABA exocytosis in a 8-Br-cAMP-sensitive. AMN082-inhibitory effect was additive to that caused by (−)baclofen, but insensitive to the GABAB antagonist 3-[[(3,4-Dichlorophenyl)methyl]amino]propyl] diethoxymethyl) phosphinic acid (CGP52432). Conversely, (−)baclofen-induced inhibition of GABA exocytosis was insensitive to MMPIP. Finally, the forskolin-evoked [3H]GABA release was reduced by AMN082 or (−)baclofen but abolished when the two agonists were added concomitantly. Mouse hippocampal synaptosomal plasmamembranes posses mGlu7 receptor proteins; confocal microscopy analysis unveiled that mGlu7 proteins colocalize with syntaxin-1A (Stx-1A), with vesicular GABA transporter (VGAT)-proteins and with GABAB receptor subunit proteins. We propose that presynaptic inhibitory mGlu7 heteroreceptors, negatively coupled to AC-dependent intraterminal pathway, exist in mouse hippocampal GABA-containing terminals, where they colocalize, but do not functionally cross-talk, with GABAB autoreceptors. This article is part of a Special Issue entitled ‘Metabotropic Glutamate Receptors’." @default.
• W2023391749 created "2016-06-24" @default.
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• W2023391749 date "2013-03-01" @default.
• W2023391749 modified "2023-10-02" @default.
• W2023391749 title "Presynaptic mGlu7 receptors control GABA release in mouse hippocampus" @default.
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• W2023391749 doi "https://doi.org/10.1016/j.neuropharm.2012.04.020" @default.
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