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Titolo:
THE GLUTAMATE RECEPTOR NO/CYCLIC GMP PATHWAY IN THE HIPPOCAMPUS OF FREELY MOVING RATS - MODULATION BY CYCLOTHIAZIDE, INTERACTION WITH GABA AND THE BEHAVIORAL CONSEQUENCES/
Autore:
FEDELE E; CONTI A; RAITERI M;
Indirizzi:
UNIV GENOA,INST PHARMACOL & PHARMACOGNOSY,VIALE CEMBRANO 4 I-16148 GENOA ITALY UNIV GENOA,INST PHARMACOL & PHARMACOGNOSY I-16148 GENOA ITALY
Titolo Testata:
Neuropharmacology
fascicolo: 10, volume: 36, anno: 1997,
pagine: 1393 - 1403
SICI:
0028-3908(1997)36:10<1393:TGRNGP>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; METHYL-D-ASPARTATE; SOLUBLE GUANYLYL CYCLASE; CENTRAL-NERVOUS-SYSTEM; NON-NMDA RECEPTORS; CYCLIC-GMP; CONCANAVALIN-A; L-ARGININE; IN-VIVO; NOREPINEPHRINE RELEASE;
Keywords:
AMPA/KAINATE RECEPTOR DESENSITIZATION; CYCLOTHIAZIDE; AMPA-NMDA RECEPTOR INTERACTION; NITRIC OXIDE (NO); CGMP; GABA-GLUTAMATE INTERACTION; MICRODIALYSIS; HIPPOCAMPUS; EPILEPSY;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
66
Recensione:
Indirizzi per estratti:
Citazione:
E. Fedele et al., "THE GLUTAMATE RECEPTOR NO/CYCLIC GMP PATHWAY IN THE HIPPOCAMPUS OF FREELY MOVING RATS - MODULATION BY CYCLOTHIAZIDE, INTERACTION WITH GABA AND THE BEHAVIORAL CONSEQUENCES/", Neuropharmacology, 36(10), 1997, pp. 1393-1403

Abstract

Monitoring of extracellular cGMP during intracerebral microdialysis in freely moving rats permits the study of the functional changes occurring in the glutamate receptor/nitric oxide (NO) synthase/guanylyl cyclase pathway and the relationship of these changes to animal behaviour. When infused into the rat hippocampus in Mg2+-free medium, cyclothiazide, a blocker of desensitization of the AMPA-preferring receptor, increased cGMP levels. The effect of cyclothiazide (300 mu M) was abolished by the NO synthase inhibitor L-NARG (100 mu M) or the soluble guanylyl cyclase inhibitor ODQ (100 mu M). During cyclothiazide infusion the animals displayed a pre-convulsive behaviour characterized by frequent ''wet dog shakes'' (WDS). Neither L-NARG nor ODQ decreased the WDSepisodes. Both cGMP and WDS responses elicited by cyclothiazide were prevented by blocking NMDA receptor function with the glutamate site antagonist CGS 19755 (100 mu M), the channel antagonist MK-801 (30 mu M) or Mg2+ ions (1 mM). The AMPA/kainate receptor antagonists DNQX (100mu M) and NBQX (100 mu M) abolished the WDS episodes but could not inhibit the cyclothiazide-evoked cGMP response. DNQX or NEQX (but not MK-801) elevated, on their own, extracellular cGMP levels. The cGMP response elicited by the antagonists appears to be due to prevention of a glutamate-dependent inhibitory GABAergic tone, since infusion of bicuculline (50 mu M) caused a strong cGMP response. The results suggest that (a) AMPA/kainate receptors linked to the NO/cGMP pathway in the hippocampus (but not NMDA receptors) are tonically activated and kept in a desensitized state by endogenous glutamate; (b) blockade of AMPA/kainate receptor desensitization by cyclothiazide leads to endogenous activation of NMDA receptors; (c) the hippocampal NO/cGMP system is undera GABAergic inhibitory tone driven by non-NMDA ionotropic receptors; (d) the pre-convulsive episodes observed depend on hippocampal NMDA receptor activation but not on NO and cGMP production. (C) 1997 ElsevierScience Ltd.

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Documento generato il 15/07/20 alle ore 13:47:59