Cis 3-Aminocyclohexane Carboxylic Acid, a Selective Inhibitor and Substrate for the Neuronal GABA Uptake Process

Abstract

GABA which is now generally believed to be an important inhibitory synaptic transmitter substance in the vertebrate central nervous system (see Krnjevic 1974) is thought to be inactivated after its release from nerve terminals by uptake processes which are present in some neurones and glia (see Iversen & Kelly, 1975). These transport processes for GABA in neurones and glia have very similar properties but can be distinguished by their structural requirements (Bowery et al, 1976). We have found that a conformationally-restricted analogue of GABA, cis 3-aminocyclohexane carboxylic acid (ACHC), which has previously been reported to competitively inhibit GABA transport in slices of cerebral cortex (Beart et al, 1972), is a relatively selective inhibitor of neuronal GABA transport (Bowery et al, 1 976). Studies with radiolabeled ACHC (3H-ACHC) indicate that the analogue is a selective substrate for the neuronal GABA transport process.