Stimulatory and inhibitory actions of excitatory amino acids on inositol phospholipid metabolism in rabbit retina. Evidence for a specific quisqualate receptor subtype associated with neurones.
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 microM. 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 microM. The NMDA action was abolished by APV, whereas this antagonist had no effect on the action of kainate.(ABSTRACT TRUNCATED AT 250 WORDS)
Osborne
N N
NN
Nuffield Laboratory of Ophthalmology, University of Oxford, U.K.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007051:Ibotenic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D016202:N-Methylaspartate; D009638:Norepinephrine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D011817:Rabbits; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000378:metabolism*
D007295:Inositol Phosphates; D010069:Oxadiazoles; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter; D007051:Ibotenic Acid; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D002217:Carbachol; D007608:Kainic Acid; D002118:Calcium; D009638:Norepinephrine