Histocytochemical study of cell death in mice cortical area after callosotomy

We have studied the effects of drugs which manipulate nitric oxide (NO) levels as well the effect of N-methyl-d-aspartate (NMDA) infusion on extracellular taurine in rat hippocampus using in vivo microdialysis. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) increased dialysate taurine in a concentration-dependent manner, and this effect was blocked by the inhibitor of soluble guanylate cyclase1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ). NMDA (100 μM) increased hippocampal taurine release, an effect that was reversed by the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5; 10 μM). The non-selective nitric oxide synthase (NOS) inhibitor N-nitro-l-arginine methyl ester (l-NAME; 100 μM and 1.0 mM) increased extracellular taurine in a concentration-dependent manner while 7-nitroindazole (7-NI), a relatively selective neuronal NOS (nNOS) inhibitor, at the same concentrations decreased extracellular taurine. l-NAME (1.0 mM) infused prior to NMDA did not alter the effect of NMDA on extracellular taurine having an effect essentially identical to that seen with l-NAME infused alone. In contrast, when 7-NI was infused for 30 min prior to NMDA, taurine levels were no longer increased above basal. This suggests to us that taurine efflux is mediated by two different mechanisms: an NMDA-evoked, 7-NI-sensitive pathway which may be dependent on cyclic guanosine monophosphate formation, and an l-NAME-modulated mechanism which presumably involves other members of the NOS group of enzymes than nNOS alone.