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Titolo:
beta-NAAG rescues LTP from blockade by NAAG in rat dentate gyrus via the type 3 metabotropic glutamate receptor
Autore:
Lea, PM; Wroblewska, B; Sarvey, JM; Neale, JH;
Indirizzi:
Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA Uniformed Serv Univ Hlth Sci Bethesda MD USA 20814 Bethesda, MD 20814 USA Uniformed Serv Univ Hlth Sci, Dept Physiol, Bethesda, MD 20814 USA Uniformed Serv Univ Hlth Sci Bethesda MD USA 20814 Bethesda, MD 20814 USA Georgetown Univ, Dept Biol, Washington, DC 20057 USA Georgetown Univ Washington DC USA 20057 pt Biol, Washington, DC 20057 USA
Titolo Testata:
JOURNAL OF NEUROPHYSIOLOGY
fascicolo: 3, volume: 85, anno: 2001,
pagine: 1097 - 1106
SICI:
0022-3077(200103)85:3<1097:BRLFBB>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
LONG-TERM POTENTIATION; N-ACETYLASPARTYLGLUTAMATE IMMUNOREACTIVITY; CEREBELLAR GRANULE CELLS; ENHANCED CARBODIIMIDE FIXATION; ACIDIC DIPEPTIDASE ACTIVITY; CYCLIC-AMP LEVELS; GROUP-III MGLURS; HIPPOCAMPAL SLICES; OLFACTORY-BULB; PERFORANT PATH;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
72
Recensione:
Indirizzi per estratti:
Indirizzo: Sarvey, JM Uniformed Serv Univ Hlth Sci, Dept Pharmacol, 4301 Jones BridgeRd, Bethesda, MD 20814 USA Uniformed Serv Univ Hlth Sci 4301 Jones Bridge Rd Bethesda MD USA 20814
Citazione:
P.M. Lea et al., "beta-NAAG rescues LTP from blockade by NAAG in rat dentate gyrus via the type 3 metabotropic glutamate receptor", J NEUROPHYS, 85(3), 2001, pp. 1097-1106

Abstract

N-Acetylaspartylglutamate (NAAG) is an agonist at the type 3 metabotropic glutamate receptor (mGluR3), which is coupled to a Gi/o protein. When activated, the mGluR3 receptor inhibits adenylyl cyclase and reduces the cAMP-mediated second-messenger cascade. Long-term potentiation (LTP) in the medialperforant path (MPP) of the hippocampal dentate gyrus requires increases in cAMP. The presence of mGluR3 receptors and NAAG in neurons of the dentategyrus suggests that this peptide transmitter may inhibit LTP in the dentate gyrus. High-frequency stimulation (100 Hz; 2 s) of the MPP resulted in LTP of extracellularly recorded excitatory postsynaptic potentials at the MPP-granule cell synapse of rat hippocampal slices. Perfusion of the slice with NAAG (50 and 200 muM) blocked LTP. Neither 50 nor 200 muM NAAG produced N-methyl-D-aspartate receptor currents in the granule cells of the acute hippocampal slice. The group II mGluR antagonist ethyl glutamate (100 mM) and a structural analogue of NAAG, beta -NAAG (100 muM), prevented the blockadeof LTP by NAAG. Paired-pulse depression of the excitatory postsynaptic potential at 20- and 80-ms interpulse intervals (IPI) was not affected by NAAGor beta -NAAG. beta -NAAG did not affect inositol trisphosphate productionstimulated by the agonist glutamate in cells expressing the group I mGluR1alpha or mGluR5. beta -NAAG blocked the decrease in forskolin-stimulated cAMP by the group II mGluR agonist (2S, 2'R, 3'R)-2-(2', 3'-dicarboxycyclopropyl) glycine (DCG-IV) but not the group III mGluR agonist L(+)-2- amino-4-phosphonobutyric acid in cerebellar granule cells. In cells transfected with mGluR3, but not mGluR2, beta -NAAG blocked forskolin-stimulated cAMP responses to glutamate, NAAG, the nonspecific group I, II agonist trans-ACPD, and the group II agonist DCG-IV. We conclude that beta -NAAG is a selective mGluR antagonist capable of differentiating between mGluR2 and mGluR3 subtypes and that the mGluR3 receptor functions to regulate activity-dependent synaptic potentiation in the hippocampus.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 19:35:30