http://www.cnr.it/ontology/cnr/individuo/prodotto/ID212569

Presynaptic mGlu7 receptors control GABA release in mouse hippocampus (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

Presynaptic mGlu7 receptors control GABA release in mouse hippocampus (Articolo in rivista) (literal)

Anno

2013-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1016/j.neuropharm.2012.04.020 (literal)

Alternative label

Summa M; Di Prisco S; Grilli M; Usai C; Marchi M; Pittaluga A (2013)
Presynaptic mGlu7 receptors control GABA release in mouse hippocampus
in Neuropharmacology; Pergamon-Elsevier Science Ltd., Oxford (Regno Unito)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Summa M; Di Prisco S; Grilli M; Usai C; Marchi M; Pittaluga A (literal)

Pagina inizio

215 (literal)

Pagina fine

224 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

http://www.sciencedirect.com/science/article/pii/S0028390812001566 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

66 (literal)

Rivista

Neuropharmacology (Rivista)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Department of Experimental Medicine, Pharmacology and Toxicology Section, University of Genoa, viale Cembrano 4, 16148 Genoa, Italy; Institute of Biophysics, National Research Council, via De Marini 6, 16149 Genoa, Italy; Center of Excellence for Biomedical Research, University of Genoa, viale Benedetto XV, 16132 Genoa, Italy (literal)

Titolo

Presynaptic mGlu7 receptors control GABA release in mouse hippocampus (literal)

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-?-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 ?M), 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. (literal)

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