Selective blockade of type-1 metabotropic glutamate receptors induces neuroprotection by enhancing gabaergic transmission. (Articolo in rivista)

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  • Selective blockade of type-1 metabotropic glutamate receptors induces neuroprotection by enhancing gabaergic transmission. (Articolo in rivista) (literal)
Anno
  • 2001-01-01T00:00:00+01:00 (literal)
Alternative label
  • Battaglia G1, Bruno V1, Pisani A2,3, Centonze D2,3, Catania MV4, Calabresi P2,3, Nicoletti F1,5. (2001)
    Selective blockade of type-1 metabotropic glutamate receptors induces neuroprotection by enhancing gabaergic transmission.
    in Molecular and cellular neurosciences (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Battaglia G1, Bruno V1, Pisani A2,3, Centonze D2,3, Catania MV4, Calabresi P2,3, Nicoletti F1,5. (literal)
Pagina inizio
  • 1071 (literal)
Pagina fine
  • 1083 (literal)
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  • 17 (literal)
Rivista
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  • By using novel subtype-selective mGlu1 and mGlu5 receptor antagonists, CPCCOOet and MPEP respectively, we report that mGlu1 and mGlu5 receptors influence neuronal degeneration via two distinct mechanims and that selective blockade of mGlu1 receptors produces neuroprotection by enhancing GABAergic transmission. We expect that selective mGlu1 receptor antagonists are particularly beneficial for the treatment of disorders in which neurodegeneration results from an impairment of synaptic inhibition as observed, for example, in the Ammon’s horn sclerosis (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1I.N.M. Neuromed, Pozzilli, Italy. 2 Clinica Neurologica, University “ Tor Vergata”, Roma, Italy 3 Fondazione Santa Lucia, IRCCS, Roma , Italy. 4 IBFSNC, CNR, Catania, Italy (ora ISN sezione di Catania) 5 Department of Human Physiology and Pharmacology, University “La Sapienza”, Roma, Italy. (literal)
Titolo
  • Selective blockade of type-1 metabotropic glutamate receptors induces neuroprotection by enhancing gabaergic transmission. (literal)
Abstract
  • Selective antagonists of mGlu1 (LY367385 and CPCCOEt) and mGlu5 (MPEP) metabotropic glutamate receptors were neuroprotective against NMDA toxicity when either applied to mixed cortical cultures or locally infused into the caudate nucleus. Neuroprotection produced by LY367385 or CPCCOEt was occluded by GABA and was abolished by a cocktail of GABA(A) and GABA(B) receptor antagonists. In contrast, GABAergic drugs did not influence the action of MPEP. In microdialysis studies, LY367385 and CPCCOEt substantially enhanced GABA release in the corpus striatum of freely moving animals, whereas MPEP had no effect on GABA but abolished the stimulation of glutamate release induced by NMDA. A role for mGlu1 receptors in modulating GABAergic transmission was supported by electrophysiological studies carried out in cortico-striatal slices. In this particular model, the mixed mGlu1/5 receptor agonist, DHPG, reduced bicuculline-sensitive inhibitory postsynaptic currents presumably via a presynaptic mechanism. The action of DHPG was antagonized by LY367385, but not by MPEP. Taken together, these results indicate that selective blockade of mGlu1 receptors produces neuroprotection by enhancing GABAergic transmission. (literal)
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