Metabolic inhibitors and subcellular distribution of GABA

Abstract

Experimental procedures are described which are believed to yield results that reflect, within certain limits, the in vivo changes of the size of the GABA pool in nerve endings in comparison with those of all other GABA pools. Two irreversible GABA-T inhibitors, vinyl GABA and acetylenic GABA, two GAD inhibitors, 3-mercaptopropionic acid and pyridoxal phosphate glutamyl-gamma-hydrazone, and di-n propylacetate, a clinically useful anticonvulsant, have been studied to determine their effects on GABA compartmentalization in mouse brain cortex. The changes elicited by these drugs in subcellular fractions of brain cortex homogenates support the notion that measurement of amino acid concentrations in crude synaptosomal fractions and in supernatant fractions under controlled conditions allow one to draw conclusions about relative changes of pool sizes in vivo. In particular this work showed that a specific increase in the concentration of GABA within the nerve endings is more important than a large increase of total brain GABA as a means of decreasing susceptibility to a variety of chemically or physically induced seizures.