Alkyl-substituted gamma-butyrolactones act at a distinct site allosterically linked to the TBPS/picrotoxinin site on the GABAA receptor complex.

K D Holland, M G Bouley, D F Covey, J A Ferrendelli

Index: Brain Res. 615(1) , 170-4, (1993)

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Abstract

Effects of alkyl-substituted gamma-butyrolactones and gamma-thiobutyrolactones on [35S]t-butylbicyclophosphorothionate (35S-TBPS) dissociation from the picrotoxinin receptor were studied. Unlike picrotoxinin, 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 gamma-butyrolactones may result from their action at a distinct site on the gamma-aminobutyric acid (GABA)A receptor.