Cross-talk between glutamate and nucleotide receptors in cerebellar granule neurons in culture

  1. Salas, Elvira 1
  2. León Navarro, David Agustín 1
  3. Sánchez Nogueiro, Jesús 1
  4. Marín García, Patricia 1
  5. Miras Portugal, María Teresa 1
  1. 1 Facultad de Veterinaria, Universidad Complutense de Madrid
Zeitschrift:
Anales de la Real Academia Nacional de Farmacia

ISSN: 1697-4298 0034-0618

Datum der Publikation: 2010

Nummer: 1

Seiten: 3-22

Art: Artikel

Andere Publikationen in: Anales de la Real Academia Nacional de Farmacia

Zusammenfassung

ATP elicits Ca2+ transients in cultured cerebellar granule neurons acting through specific ionotropic (P2X) and metabotropic (P2Y) purinergic receptors. In these neurons, application of L-Glutamate (L-Glu) immediately before ATP induced a prolonged reduction of ATP-mediated responses that remains at least 5 minutes after L-Glu wash out. alpha-amino-3-hydro-5-methyl-4-isoxazolpropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and 3,5-dihydroxyphenyl-glycine (DHPG), selective agonists of ionotropic non-NMDA, NMDA and Group I metabotropic glutamate receptors respectively, mimicked Glu-induced attenuating effects. The activity of calcium-calmodulin dependent protein kinase II (CaMKII) seems to be involved, at least at long term, because inhibitors of CaMKII, 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4phenylpiperazine (KN-62) and N-[2-[[[3-(4'-chlorophenyl)-2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4'-methoxybenzenesulfonamide (KN-93), abolished the inhibitory effect of L-Glu on ATP-mediated responses. However, it is likely that other protein kinases could be involved in the cross-talk process between both groups of receptors at short term. Therefore, these results demonstrate that the activation of glutamate receptors is able to modulate nucleotide responses in cerebellar granule neurons.

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