Age-related effects of NMDA-stimulated concomitant release of nitric oxide and glutamate in cortical slices prepared from DBA/2 mice.
In this study we have used cortical slices prepared from genetically epilepsy-prone DBA/2 mice to investigate the effects of N-methyl-D-aspartate (NMDA) receptor stimulation on the concomitant release of nitric oxide (NO) and endogenous amino acids. DBA/2 mice exhibit an age-related susceptibility to audiogenic seizures so consequently we have compared the responses in 14-16-, 21-30- and 56-63-day-old mice. NMDA (200 microM) stimulated the release of NO and glutamate in slices prepared from 21-30-day-old animals. The release of both NO and glutamate was inhibited by the NO synthase inhibitor, L-NG-monomethylarginine (L-NG-MMA), and by haemoglobin. There was no significant NMDA-stimulated release of NO or glutamate in slices prepared from 14-16- or 56-63-day-old mice. These results support a neuromodulator role for NO in the release of transmitter and also provide evidence that the age-related susceptibility of DBA/2 mice to audiogenic seizures is related to changes in sensitivity to NMDA receptor-mediated events.
Rowley
H L
HL
Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Ellis
Y
Y
Davies
J A
JA
D000161:Acoustic Stimulation; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016202:N-Methylaspartate / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D012640:Seizures / Q000235:genetics* / Q000378:metabolism
D005971:Glutamates; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate