S. K. Fisher’s research while affiliated with University of Birmingham and other places

Abstract—The possible existence of GABA-transmitter neurons in the lower auditory system of the guinea pig has been investigated by means of three different experimental approaches: (1) the regional distribution of GABA and its related enzymes. (2) the subcellular distribution of glutamate decarboxylase, and (3) the effect of selected nerve lesions on glutamate decarboxylase concentrations in the auditory nuclei. Within the regions investigated considerable variations in glutamate decarboxylase activity and GABA concentration were found, with the highest values observed in the inferior colliculus. The dorsal cochlear nucleus also contained significant amounts of both glutamate decarboxylase and GABA, in addition to high concentrations of GABA transaminase. The subcellular distribution of glutamate decarboxylase was bimodal in both the cochlear nucleus and inferior colliculus with most enzyme activity recovered in the soluble and synaptosomal fractions. Neither end organ (cochlea) nor trapezoid body lesions induced a significant loss of glutamate decarboxylase activity in either the cochlear nucleus or inferior colliculus. The results suggest the presence of short axon GABAergic interneurons in the cochlear nucleus, most of which appear to terminate within the dorsal cochlear nucleus.

—Glutamate decarboxylase (l-glutamate 1-carboxy-lyase EC 4.1.1.15; GAD) has been isolated from guinea pig brain and some of its properties studied. Many of its properties indicated that it was similar if not identical to the decarboxylase isolated from other species. It showed normal Michaelis-Menten kinetics (Km= 8 mM), had a pH optimum of 6.6–7.0 and was protected by sulphydryl reagents. Its activity was stimulated by pyridoxal phosphate and inhibited by a variety of anions, cations and carbonyl trapping agents. Allylglycine strongly inhibited GAD isolated from the brains of several different species. The mechanism of this inhibition has been studied kinetically and compared to chloride induced inhibition. The kinetic data presented is consistent with the idea that allylglycine inhibits the enzyme by a partially reversible inactivation rather than by reversible competitive inhibition.