TBPS Binding to the GABA/Benzodiazepine Receptor Complex in Cultured Cerebellar Granule Cells

Abstract

t-Butylbicyclophosphorothionate (TBPS) is a byciclophosphate derivative with potent picrotoxin-like convulsant activity that binds with high affinity and specificity to a Cl^- channel modulatory site of the GABA/benzodiazepine receptor complex (Squires and Casida 1983). Using intact and differentiated cerebellar granule cells maintained in culture (Kingsbury et al. 1985), we have studied the modifications induced by GABA and diazepam on the ion channel modulatory binding site labeled by (³⁵S)TBPS. Both autoradiographic (Mohler et al. 1981) and biochemical studies (Allen and Dutton 1984) have previously indicated that cerebellar granule cells possess a high density of GABA and benzodiazepine receptors in vivo or in culture. Granule cell-enriched primary cultures and their crude membrane preparations show both GABA and benzodiazepine high affinity, saturable binding sites (Meier and Schousboe 1982).