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

ATP elicits Ca 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 calciumcalmodulin dependent protein kinase II (CaMKII) seems to be involved, at least at long term, because inhibitors of CaMKII, 1-[N,Obis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4phenylpiperazine DAVID LEÓN NAVARRO Y COLS. AN. R. ACAD. NAC. FARM. 4 (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.