Comparative pharmacological actions of N‐acetylcysteine and L‐cysteine on excitatory neurotransmission in bovine isolated retina (1060.4)

Abstract

There is evidence that L‐cysteine, the substrate for biosynthesis of hydrogen sulfide (H2S) can regulate potassium (K+)‐evoked glutamate release from bovine isolated retina. In the present study, we compared the pharmacological effects of the precursor for L‐cysteine, N‐acetyl cysteine (NAC) to that of L‐cysteine on K+‐evoked [3H]D‐aspartate release, and on glutamate‐induced neurotoxicity in bovine isolated retina. Isolated neural retina were incubated in oxygenated Krebs solution containing 200 nM of [3H]D‐aspartate and then prepared for studies of neurotransmitter release. The 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay was used to assess retinal neuron survival. Both L‐cysteine (0.1 µM to 10 µM) and NAC (10 µM to 1 mM) elicited a concentration‐dependent inhibition of K+‐induced [3H]D‐aspartate release. At an equimolar concentration of 10 µM, both L‐cysteine and NAC reduced [3H]D‐aspartate release by 54.3% (p < 0.001) and 8.3%, respectively. Interestingly, L‐cysteine (1 mM) and NAC (1 µM) attenuated glutamate (12 mM)‐induced neuron degeneration by 31.1% (p<0.05) and 18.4%, respectively. L‐cysteine was more potent in attenuating neurotransmitter release while NAC was more effective in preventing glutamate‐induced toxicity suggesting that these compounds mediate their pharmacological actions via different mechanisms.