Cerebral glutamine metabolism: study of modulatory effects of glutamine on gamma-aminobutyric acid-ergic neurotransmission.
Glutamine is one major precursor of gamma-aminobutyric acid (GABA) and glutamate, the most important inhibitory and excitatory neurotransmitters in the mammalian brain, respectively. Changes in cerebral glutamine concentrations occur in various metabolic encephalopathies including hyperammonemia and liver failure. As glutamine inhibits the specific binding of GABA to its postsynaptic receptor at physiologic concentrations, in this study the effects of glutamine on various components of the GABAA-benzodiazepine receptor complex were studied. Glutamine dose dependently inhibited the stimulation of flunitrazepam binding by GABA. This inhibition occurred already at concentrations of 10 mumol/L glutamine. Glutamine had no effects on basal or GABA-stimulated synaptoneurosomal chloride uptake. It is concluded that glutamine is not a modulator of the GABAA-benzodiazepine neurotransmitter system. Thus, changes of cerebral glutamine concentrations are unlikely to contribute to the activation of GABA-ergic neurotransmission in liver failure.
Ferenci
P
P
First Department of Gastroenterology and Hepatology, University of Vienna, Austria.
Zimmermann
C
C
Ebner
J
J
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002712:Chlorides; D011963:Receptors, GABA-A; D005973:Glutamine; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam