Age-dependent variation in the sensitivity of rat brain glutamine synthetase to L-methionine-DL-sulfoximine.
Effects of a subacute dose (150 mg/kg body wt) of methionine sulfoximine was studied on the behavioural changes and glutamine synthetase activity in cerebral cortex, cerebellum and brain stem of rats of four different age groups. Animals of 10 days and 90 days age groups were less vulnerable to the toxic effects of methionine sulfoximine. Rats of 180 days age exhibited various behavioural changes upon the administration of methionine sulfoximine and entered into convulsions at the end of 17 hr. In rats of 360 days age group these changes appeared quite early and the animals convulsed at the end of 13 hr. Animals of these two age groups failed to recover from toxic effects of methionine sulfoximine. Methionine sulfoximine inhibited glutamine synthetase activity in the brains of rats of all age groups. Maximum inhibition of activity was noticed at the end of 12 hr in 10-day-old rats while in the animals of other age groups it was seen at the end of 3 hr. In animals of all age groups the enzyme activity was inhibited by 60-70% except in 360-day-old rats where the inhibition was 95%. Behavioural changes and inhibition of glutamine synthetase were out of phase with each other. It is suggested that the toxicity of methionine sulfoximine may not be due to its effect on glutamine synthetase alone. Further, these results also suggest that the toxic effects of methionine sulfoximine vary with the age of the animal.
Rao
V L
VL
School of Life Sciences, University of Hyderabad, India.
Murthy
C R
CR
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008717:Methionine Sulfoximine / Q000633:toxicity*; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009498:Neurotoxins; D008717:Methionine Sulfoximine; D005974:Glutamate-Ammonia Ligase