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Effects of Gabaculine on the uptake, binding and metabolism of GABA
R D Allan1, G A Johnston, B Twitchin
1Department of Pharmacology, Australian National University, Canberra Australia.
Abstract:
Gabaculine, a conformationally restricted analogue of GABA, is (i) a moderately potent inhibitor (IC(50) 69 muM) of the sodium-dependent uptake of GABA in rat brain slices, (ii) ineffective at 100 muM as an inhibitor of the sodium-independent binding of GABA to membranes from rat brain, (iii) a relatively weak inhibitor (IC(50) > 1 mM) of glutamate decarboxylase activity in tracts of rat brain, and (iv) a very potent inhibitor (IC(50) 3 muM) of the transamination of GABA catalyzed by extracts of rat brain mitochondria. Inhibition of transamination is time-dependent and follows pseudo-first order kinetics, which is consistent with gabaculine acting as a catalytic inhibitor at the active site.
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