Db. Goodnough et Je. Hawkinson, NEUROACTIVE STEROID MODULATION OF [H-3] MUSCIMOL BINDING TO THE GABA(A) RECEPTOR COMPLEX IN RAT CORTEX, European journal of pharmacology. Molecular pharmacology section, 288(2), 1995, pp. 157-162
Epalons are a subclass of neuroactive steroids which are positive allo
steric modulators of the GABA(A) receptor acting via a unique site on
the receptor complex. Enhancement of [H-3]muscimol binding to the GABA
recognition site was observed to be either full (> 150%) or limited (
110-135%) and specific for epalons. Both one and two component modulat
ion was observed. Saturation studies performed in the presence of 3 al
pha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-P) showed that 3 a
lpha,5 alpha-P increased the density of high affinity [H-3]muscimol si
tes and doubled the affinity of low affinity sites. 3 alpha,5 alpha-P
had no effect on the affinity of the high affinity site or the density
of the low affinity site. These data indicate that: (1) epalons are p
otent, stereoselective enhancers of [H-3]muscimol binding; (2) epalons
display varying levels of efficacy and some exhibit two-component enh
ancement; and (3) 3 alpha,5 alpha-P enhancement of [H-3]muscimol bindi
ng results from both an increased density of high affinity sites and a
n increased affinity for low affinity sites.