Isoguvacine Binding, Uptake, and Release: Relation to the GABA System

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Abstract
Isoguvacine (1,2,3,6-tetrahydropyridine-4-carboxylic acid) is a GABA agonist with limited conformational flexibility. In these studies we investigated the binding uptake, and release of [3H] isoguvacine by use of tissue preparations of rat CNS, comparing the results with similar studies of [3H]GABA. The results indicate that isoguvacine binds to membrane preparations of rat forebrain with pharmacological characteristics similar to the postsynaptic GABA recognition site; that it is transported into synaptosomal preparations by an uptake system similar to the high-affinity GABA uptake system; and that recently accumulated isoguvacine is released in a Ca2+-dependent manner and by heteroexchange with external GABA. The ability of isoguvacine and .gamma.-hydroxybutyric acid to decrease the K+-stimulated Ca2+-dependent release process was also investigated. Apparently, isoguvacine interactions have many of the biochemical features of GABA synaptic function, but isoguvacine is less potent than GABA.