Factor I and GABA: Resolution of a long-standing problem

Abstract

1. 1. Factor I, the inhibitory agent(s) present in certain nerve extracts which is responsible for the inhibition of crayfish stretch receptor neurones, is up to 300 times more effective than can be accounted for by the contained γ-aminobutyric acid (GABA). 2. 2. The inhibition caused by extracts of crab nerves is almost exclusively due to amino acids (aspartate, glutamate, taurine) other than GABA, except in the case of extracts of isolated inhibitory axons. 3. 3. The sensitivity of stretch receptor neurones to aspartate, glutamate and taurine varies independently from that to GABA. As a result of this, there are great quantitative variations in the inhibitory effects of nerve extracts. 4. 4. The mechanism of action of aspartate, glutamate and taurine appears to be the same as that of GABA: all these amino acids activate Cl channels and their action can be blocked by picrotoxin. 5. 5. When tested on the isolated hindgut of the vas deferens of crayfish, aspartate, glutamate and taurine can act like GABA. 6. 6. Extracts of mammalian brain contain a far greater proportion of GABA than do crustacean nerve extracts. GABA thus accounts for about 35 per cent of the inhibitory effect of the brain extracts. Aspartate, glutamate and taurine account for another 30 per cent. The remainder-according to other authors-is due to guanidino compounds, possibly also to γ-amino-β-hydroxybutyric acid. 7. 7. An extensive discussion resolves apparent contradictions in the literature concerning the identity and significance of Factor I, and its relation to GABA.