Kinetic analysis of the accumulation of gamma-aminobutyric acid by particulate fractions of rat brain: comparison of the effects of nipecotic acid and cis-3-aminocyclohexane-1-carboxylic acid.

Kinetic analyses indicate that nipecotic acid and cis-3-aminocyclohexane-1-carboxylic acid (cis-3-ACHC) inhibit GABA accumulation by similar mechanisms of action. Both amino acids are competitive inhibitors of particulate GABA accumulation when GABA and the inhibitor are added simultaneously to tissue fractions. However, preincubating the tissue with either amino acid produces noncompetitive inhibition of GABA accumulation at low concentrations of inhibitor and mixed inhibition at higher concentrations. The possible roles of intrasynaptosomal mechanisms and of astroglia in producing these effects are discussed. The most notable difference between cis-3-ACHC and the other amino acid inhibitors of GABA accumulation, such as nipecotic acid, cis-4-OH-nipecotic acid, guvacine, beta-proline, homo-beta-proline, and 2,4-diaminobutyric acid (DABA), is that cis-3-ACHC is approximately 3.5 times more potent as an inhibitor following preincubation. Thus, while cis-3-ACHC does inhibit GABA transport, its major site of action in the synaptosome may be intracellular.