The metabolism of gamma-aminobutyric acid (GABA) in the lobster nervous system--uptake of GABA in the nerve-muscle preparations |
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Authors: | L L Iversen E A Kravitz |
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Institution: | 1. Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, U.S.A.
Harkness Fellow. Present address: Department of Pharmacology, Cambridge University, Cambridge, England.;2. Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, U.S.A. |
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Abstract: | The lack of information on the mechanism of inactivation of the crustacean neuromuscular inhibitory transmitter compound prompted a study of the disposition of radioactive γ-aminobutyric acid (GABA) in lobster nerve-muscle preparations. A specific GABA transport system was found. Radioactive GABA was concentrated by the tissues to levels several times those in the medium, and net uptake could be demonstrated. The process was dependent on sodium ions in the medium; neither lithium nor choline could substitute for sodium. Incubations with increasing GABA concentrations indicated that uptake was a saturable mechanism with an apparent Km of 5.8 × 10?5m . Of many compounds tested, only desmethylimipramine, chlopromazine (and several related compounds), and certain close structural analogues (guanidinoacetic acid, β-guani-dinopropionic acid and,β-hydroxy-GAB A) were effective inhibitors of uptake. The inhibition with all these compounds, however, was at high concentrations (5 × 10?4 to 10?3m ) which limited their usefulness for physiological studies. A separate uptake mechanism for glutamate was found in the lobster nerve-muscle preparations. This process was not described in detail, but certain properties are similar to those of the GABA transport system. The cellular location of the GABA uptake system remains unknown. By analogy with noradrenaline inactivation, however, it is postulated that uptake could serve to terminate the physiological actions of GABA by rapidly removing it from its sites of action in synaptic clefts. |
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