Gamma-aminobutyric acidA receptor complexes in rat frontal cortex and spinal cord show differential responses to steroid modulation

Abstract

Regional differences in neuroactive steroid modulation of the gamma-aminobutyric acidA receptor-chloride ionophore complex (GBRC), as measured by t-butylbicyclophosphoro[35S]thionate ([35S] TBPS) binding and 36Cl- uptake, were demonstrated in rat spinal cord versus frontal cortex. The rank order of potencies of a series of 5 alpha- and 5 beta-reduced isomers of 3 alpha-hydroxylated steroids against [35S]TBPS binding were different between regions. The differences in rank order of potencies imply the possible existence of heterogeneous populations of GBRC-coupled steroid recognition sites. The relative potencies of selected 5 alpha- and 5 beta-reduced isomers as potentiators of 36Cl- uptake paralleled their potencies as inhibitors of [35S]TBPS binding. Differential sensitivity of the steroid recognition site to the allosteric influence of gamma-aminobutyric acid was also demonstrated. It appears that regionally specific responses to GBRC-active steroids do occur, although the functional consequences of these effects await evaluation in appropriate in vivo models.