Inhibition of acute hyperammonemia-induced convulsions by systemically administered gamma aminobutyric acid in rats.
The present study has investigated the effects of intraperitoneally administered gamma aminobutyric acid (GABA) on ammonium chloride-induced hyperammonemia and convulsions in rats. Systemically administered GABA did not alter the concentration of GABA in the brain of control as well as hyperammonemic animals. However, hyperammonemia-induced convulsions were inhibited by GABA in a dose-dependent manner. This was accompanied by a dose-dependent decrease in the concentrations of ammonia in both blood and brain and an elevation of glutamine in the blood. These results suggest that GABA has the potential to prevent acute hyperammonemia by increasing detoxification of ammonia to glutamine. As a result, the diffusion of ammonia from blood into the brain has been decreased. This accounts for an inhibition of convulsions by systemically administered GABA in hyperammonemic animals.
Paul
Vanaja
V
Department of Pharmacology and Environmental Toxicology, Dr. ALM Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, 600 113, Chennai, India. pgibms@md2.vsnl.net.nl
D000641:Ammonia / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D022124:Hyperammonemia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007263:Infusions, Parenteral; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
D005680:gamma-Aminobutyric Acid; D000641:Ammonia