RT Journal Article
SR Electronic
T1 Gamma-aminobutyric acidA receptor complexes in rat frontal cortex and spinal cord show differential responses to steroid modulation.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 995
OP 999
VO 40
IS 6
A1 K W Gee
A1 N C Lan
YR 1991
UL http://molpharm.aspetjournals.org/content/40/6/995.abstract
AB 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.