Isoguvacine binding, uptake, and release: relation to the GABA system.
Isoguvacine (1,2,3,6-tetrahydropyridine-4-carboxylic acid) is a GABA (gamma-aminobutyric acid) 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 from these investigations indicate that isoguvacine binds to membrane preparations of rat forebrain with pharmacological characteristics similar to the post-synaptic 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. The results indicate that isoguvacine interactions have many of the biochemical features of GABA synaptic function, isoguvacine being, however, less potent than GABA.
D019325:3-O-Methylglucose; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D007539:Isonicotinic Acids / Q000378:metabolism*; D007700:Kinetics; D008757:Methylglucosides / Q000378:metabolism; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002250:Carbon Radioisotopes; D007539:Isonicotinic Acids; D008757:Methylglucosides; D014316:Tritium; D019325:3-O-Methylglucose; D005680:gamma-Aminobutyric Acid; C015300:isoguvacine