The effects of excitatory amino acid agonists on [3H]inositol phosphates (InsPs) levels have been examined in rabbit retinal tissues under basal conditions and after agonist stimulation. Quisqualate (QA) is the most effective excitatory amino acid agonist at stimulating InsPs accumulation with an EC50 value of 0·1 μm. The responses for maximally effective concentrations of QA with either ibotenate or kainate were not additive, which suggested that all the excitatory amino acid agonists which stimulate InsPs accumulation (quisqualate, kainate, NMDA, glutamate, ibotenate, aspartate) have a common site of action. None of the following antagonists: dl-2-amino-5-phosphonovalerate (APV), dl-2-amino-4-phosphonobutyrate (APB) and glutamate dimethyl ester (GDEE), prazosin, ketanserin or atropine influenced the excitatory amino agonist stimulation of InsPs. These data suggest the presence of a specific QA-receptor subtype in the retina. QA, and to a lesser extent other excitatory amino acid agonists, were also effective in stimulating InsPs accumulation and the mobilization of internal calcium levels in 3-5-day-old retinal cultures but not in the older cultures (25-30 days old), which lack neurones but contain Müller cells. The QA receptor subtypes linked to InsPs accumulation in the retina are therefore present on neurones. Kainate and NMDA had a weak inhibitory action on the effect of the carbachol-induced stimulation of InsPs at 50 μm. The NMDA action was abolished by APV, whereas this antagonist had no effect on the action of kainate. Experiments with tetrodotoxin, cadmium and verapamil indicate that the kainate and NMDA action on the carbachol-induced stimulation of InsPs does not take place through an indirect release of substances from neighbouring neurones. The mode of action of NMDA and kainate in reducing agonist-mediated InsPs formation in the retina still requires elucidation. © 1990.
