Taurine reduces ammonia- and N-methyl-D-aspartate-induced accumulation of cyclic GMP and hydroxyl radicals in microdialysates of the rat striatum.
Acute ammonia neurotoxicity caused by intraperitoneal administration of ammonium salts is mediated by overactivation of N-methyl-D-aspartate (NMDA) receptors, with ensuing generation of free radicals and extracellular accumulation of cyclic GMP (cGMP) arising from stimulation of nitric oxide (NO) synthesis. In this study, infusion of ammonium chloride or NMDA into the striata of rats via microdialysis probes increased the contents of cyclic GMP and hydroxyl radicals in the microdialysates. Co-infusion of taurine virtually abolished both the ammonia- and NMDA-induced accumulation of cGMP. Taurine also attenuated accumulation of hydroxyl radicals evoked by either treatment. This result is the first evidence of a potential of taurine to attenuate the effects of NMDA receptor overactivation by ammonia in vivo and points to the inhibition of the NMDA receptor-mediated NO synthesis as a possible mechanism of its neuroprotective action. Taurine or its blood-brain barrier penetrating analogues may be applicable in treatment of ammonia-induced neurological deficits.
Hilgier
Wojciech
W
Department of Neurotoxicology, Medical Research Centre, Polish Academy of Sciences, Pawińskiego St. 5, 02-106 Warsaw, Poland.
Anderzhanova
Elmira
E
Oja
Simo S
SS
Saransaari
Pirjo
P
Albrecht
Jan
J
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis*; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013654:Taurine / Q000494:pharmacology*
D018696:Neuroprotective Agents; D000643:Ammonium Chloride; D013654:Taurine; D017665:Hydroxyl Radical; D016202:N-Methylaspartate; D006152:Cyclic GMP