Excitatory amino acid-induced phosphoinositide hydrolysis in Müller glia.

The presence of excitatory amino acid (EAA) receptors coupled to phosphoinositide metabolism in primary cultures of Müller (glial) cells from the chick retina was established. The order of potency of analogues for stimulating [3H]inositol phosphate (IP) accumulation was quisqualate (QA) > L-glutamate (L-Glu) = kainate (KA) > N-methyl-D-aspartate (NMDA) > L-aspartate (L-Asp) with EC50 in the range of 1-100 microM. 1-Aminocyclopentane-1,3-dicarboxylate (trans-ACPD), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), 2-amino-3-phosphonopropionate (AP3), and 2-amino-4-phosphonobutyrate (AP4) showed no effect either on basal concentration or on stimulated accumulation of [3H]IPs. The effect of EAA was potently inhibited by the ionotropic NMDA receptor antagonists 2-amino-5-phosphonopentanoate (AP5), 3-[(RS)-2-carboxy-piperazin-4-yl)]-propyl-1-phosphonate (CPP), and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-10- imine (MK-801); L-Glu antagonists at non-NMDA receptors, the quinoxalines NBQX and DNQX, inhibited weakly the response to L-Glu, KA, and NMDA, and more potently that to QA. The translocation of protein kinase C was also stimulated by EAA with the same pharmacological profile, and was partially inhibited by kynurenate (KYN). L-Glu and KA induced 45Ca2+ influx, which was decreased by KYN and CNQX. EAA-induced [3H]IPs accumulation was decreased by verapamil but not by nifedipine, and slightly diminished by dantrolene. Results demonstrate that EAA-induced phosphoinositide hydrolysis in Müller cells shows pharmacological differences with that in astrocytes and neuronal cells and could be triggered by a different mechanism.