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Abstract

Effects of glial uptake and desensitization on the activity of gamma-aminobutyric acid (GABA) and its analogs at the cat dorsal root ganglion.

J P Gallagher, J Nakamura and P Shinnick-Gallagher
Journal of Pharmacology and Experimental Therapeutics September 1983, 226 (3) 876-884;
J P Gallagher
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J Nakamura
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P Shinnick-Gallagher
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Abstract

Responses to gamma-aminobutyric acid (GABA) and 13 structurally related analogs were recorded under voltage clamp conditions from isolated cat dorsal root ganglia (DRG). All of the analogs were applied by superfusion at a concentration of 1 mM. Of the 13 structurally related compounds, only muscimol was more effective than GABA in its ability to produce an inward current at the DRG membrane. Complete (1 microM-10 mM) concentration-response relationships were obtained for muscimol, GABA and 3-aminopropane sulfonic acid. Muscimol was most potent at all concentrations, however, the relative order of potency for GABA and 3-aminopropane sulfonic acid was concentration-dependent. In addition to producing differences in their peak currents, the various agonists demonstrated different time courses in their respective rates of decay. When the glial uptake system for GABA in cat DRG was inhibited by substituting lithium for sodium or by the addition of 1 mM nipecotic acid to the normal Krebs' solution, the membrane responses to GABA, SL-75102 and isoguvacine were facilitated, whereas the responses induced by the other analogs remained unchanged. Although the process of uptake altered significantly the decay phase of GABA responses when GABA was applied by superfusion or by iontophoresis, nipecotic acid inhibition of uptake did not appear to affect GABA-induced desensitization that was apparent when GABA was applied either by superfusion or with long iontophoretic pulses. GABA and all of the analogs in this study demonstrated cross-desensitization, each being able to depress the action of the other. Our results suggest that all of the active GABA analogs appear to be acting at a similar GABA receptor on cat DRG and this GABA receptor is coupled to a chloride channel.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 226, Issue 3
1 Sep 1983
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Abstract

Effects of glial uptake and desensitization on the activity of gamma-aminobutyric acid (GABA) and its analogs at the cat dorsal root ganglion.

J P Gallagher, J Nakamura and P Shinnick-Gallagher
Journal of Pharmacology and Experimental Therapeutics September 1, 1983, 226 (3) 876-884;

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Abstract

Effects of glial uptake and desensitization on the activity of gamma-aminobutyric acid (GABA) and its analogs at the cat dorsal root ganglion.

J P Gallagher, J Nakamura and P Shinnick-Gallagher
Journal of Pharmacology and Experimental Therapeutics September 1, 1983, 226 (3) 876-884;
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