Effects of alkyl-substituted γ-butyrolactones and γ-thiobutyrolactones on [35S]t-butylbicyclophosphorothionate (35S-TBPS) dissociation from the picrotoxinireceptor were studied. Unlike picrotoxin, these lactones accelerated the dissociation rate of 35S-TBPS. Thus, previous reports that these lactones change the Kd but not the Bmax of 35S-TBPS in equilibrium binding experiments is explained not by competitive inhibition, but by an allosteric interaction with the 35S-TBPS binding site. These results indicate that modulatory effects of alkyl-substituted γ-butyrolactones may result from their action at a distinct site on the γ-aminobutyric acid (GABA)A receptor.
- γ-Aminobutyric acid
- γ-Aminobutyric acid receptor