Interrelationships between ornithine, glutamate, and GABA. II. Consequences of inhibition of GABA-T and ornithine aminotransferase in brain.
The objective of the present study was to compare the effects of elevation of GABA concentration and those of inactivation of L-ornithine: 2-oxoacid aminotransferase (OAT) on the in vivo metabolism of L-ornithine (Orn) in brain. Vigabatrin (4-aminohex-5-enoic acid) and gabaculine (5-amino-1,3-cyclohexadienyl carboxylic acid), two well known inactivators of GABA-T, were used to elevate brain GABA concentrations. The latter inactivates OAT also. Transamination of Orn is, from a quantitative point of view, a significant reaction in mouse brain. GABA is a feed-back regulator of OAT. Within GABAergic neurons Orn concentration may be regulated by endogenous GABA. Extensive inactivation of OAT causes a considerable increase of Orn concentration, both in synaptosomes and in non-synaptosomal compartments. The results are compatible with a role of Orn as precursor of glutamate and/or GABA in certain neurons.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000614:Aminocaproates / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D008297:Male; D051379:Mice; D009952:Ornithine / Q000378:metabolism*; D009953:Ornithine-Oxo-Acid Transaminase / Q000037:antagonists & inhibitors*; D000637:Transaminases / Q000037:antagonists & inhibitors*; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000614:Aminocaproates; D003509:Cyclohexanecarboxylic Acids; D005971:Glutamates; C012987:gabaculine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D009952:Ornithine; D000637:Transaminases; D009953:Ornithine-Oxo-Acid Transaminase; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin