L. Pignataro et Sf. Deplazas, EPIPREGNANOLONE ACTS AS A PARTIAL AGONIST ON A COMMON NEUROSTEROID MODULATORY SITE OF THE GABA(A) RECEPTOR COMPLEX IN AVIAN CNS, Neurochemical research, 22(2), 1997, pp. 221-225
Neurosteroid modulatory sites present in the GABA(A) receptor complex
in chick optic lobe were investigated, in order to evaluate whether al
lopregnanolone and alphaxalone act through a common site of action. Re
sults showed that either allopregnanolone or alphaxalone present a sin
gle-component enhancement of [H-3]flunitrazepam binding with EC(50) of
1.18 +/- 0.12 and 6.56 +/- 0.86 mu M and E(max) of 82.18 +/- 5.80 and
62.98 +/- 3.73 %, respectively. Epipregnanolone behaved as a partial
agonist of these steroid modulatory sites with EC(50) of 0.49 +/- 0.15
mu M and E(max) 12.34 +/- 1.03 %. Moreover, the addition of 16 mu M e
pipregnanolone to either allopregnanolone or alphaxalone decreased EC(
50) values to 0.54 +/- 0.09 and 1.24 +/- 0.25 mu M respectively, while
E(max) values were not significantly affected. On the other hand, add
itivity experiments disclosed that a maximal concentration (16 mu M) o
f alphaxalone in the presence of allopregnanolone failed to enhance [H
-3]flunitrazepam binding in excess of that produced by allopregnanolon
e alone. Results indicate that not only allopregnanolone and alphaxalo
ne act through a common site of action, but such site is highly stereo
specific with regard to the neurosteroid spatial configuration.