Repression of glutaminase I in the rat retina by administration of sodium-L-glutamate II.

Further studies of the retinal glutamate effect have shown that not only is glutaminase I decreased in glutamate-treated rat retinas, hut glutamic-aspartic transaminase is significantly increased. Direct competitive inhibition of glutaminase I by glutamate can be demonstrated. However, studies with labeled glutamate show that under the conditions of our experiments, retinal concentrations of glutamate reach, at most, the 10 per cent inhibitory level, and that for only a short time. This increases the likelihood that the observed, effects are due to repression and induction of enzyme synthesis. u. ' nique and reproducible retinal damage has been shown to follow systemic administration of monosodium glutamate to newborn mice 1 ' 2 and rats. 3 This damage is twofold, including disappearance of the primitive ganglion cell layer along with failure of maturation of the bipolar cell layer. The tissue damage has been shown to be correlated with a loss of the b wave of the electroretinogram 2 and with severe depression of retinal glutaminase I. 3 Because glutamate is the product of the deamidating action of glutaminase I on glutamine, it seemed likely that glutamate acted through the mechanism of feedback inhibition. What was not clear was whether glutamate acted by simply inhibiting the activity of the retinal enzyme or whether it repressed the formation of the enzyme in the affected newborn retinas. Subsequent to our earlier report, 3 we have carried out studies designed to cast further light on the specific mechanism of action of glutamate in the sensitive retinas. Further assays of retinal enzyme activity have been performed. Studies were made to analyze the pattern and quantity of tissue uptake of monosodium glutamate after treatment of newborn rats of various ages. Experiments have been conducted to elucidate the type of inhibition of glutaminase I, comparing the tissue concentration of the compound in the retina with the concentration required to directly inhibit the enzyme. Methods Enzyme assays. The methods of assay of glutaminase I, the glutaminase II system, glutam