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By Ricardo Tapia (auth.), Leslie L. Iversen, Susan D. Iversen, Solomon H. Snyder (eds.)

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24 RICARDO TAPIA Roberts, 1963). , 1968). , 1971a), inhibited the uptake of GABA by isolated nerve endings (synaptosomes). , 1971). The inhibitory effect of L-2,4-diaminobutyric acid on the uptake of GABA by brain slices (Table 3) has also been reported in synaptosomal preparations (Simon and Martin, 1973). This inhibitor seems to be transported into the synaptosomes at least in part by a carrier different from that involved in GABA uptake (Simon and Martin, 1973). It might be of physiological importance (Tapia, 1974) that GAD seems to be bound to CNS membranes, including synaptosomes, synaptic vesicles, and isolated synaptosomal membranes, in the presence of Ca2 + (Fonnum, 1968; Haber and Kuriyama, 1969).

20 RICARDO TAPIA 3. l. , 1970c). Any substance that may affect the uptake of GABA is therefore of great interest for the study of the physiological role of this amino acid in the nervous system. Studies on the effect of compounds on the uptake of GABA have been carried out in brain slices or in brain subcellular fractions. Table 3 lists the compounds that have been shown to inhibit GABA uptake in brain slices, and TaBle 4 lists some of the drugs without effects. Although many substances inhibited the uptake, it seems premature to conclude that specific inhibitors of GABA uptake have been found.

1972). Since these two substances are more soluble than bicuculline, they may be very useful in PHARMACOLOGY OF GABA IN eNS 29 studies of GABA synapses. , 1972). Another substance which produces convulsions when applied topically to the cerebral cortex is d-tubocurarine. , 1972b, 1973b). On the assumption that bicuculline is indeed a specific antagonist of GABA interaction with the receptor, it is interesting that at least four compounds have been demonstrated to inhibit the firing of some CNS neurons by a bicuculline-sensitive mechanism.

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