Epipregnanolone acts as a partial agonist on a common neurosteroid modulatory site of the GABA(A) receptor complex in avian CNS.
Neurosteroid modulatory sites present in the GABA(A) receptor complex in chick optic lobe were investigated, in order to evaluate whether allopregnanolone and alphaxalone act through a common site of action. Results showed that either allopregnanolone or alphaxalone present a single-component enhancement of [3H]flunitrazepam binding with EC50 of 1.18 +/- 0.12 and 6.56 +/- 0.86 microM and Emax of 82.18 +/- 5.80 and 62.98 +/- 3.73%, respectively. Epipregnanolone behaved as a partial agonist of these steroid modulatory sites with EC50 of 0.49 +/- 0.15 microM and Emax 12.34 +/- 1.03%. Moreover, the addition of 16 microM epipregnanolone to either allopregnanolone or alphaxalone decreased EC50 values to 0.54 +/- 0.09 and 1.24 +/- 0.25 microM respectively, while Emax values were not significantly affected. On the other hand, additivity experiments disclosed that a maximal concentration (16 microM) of alphaxalone in the presence of allopregnanolone failed to enhance [3H]flunitrazepam binding in excess of that produced by allopregnanolone alone. Results indicate that not only allopregnanolone and alphaxalone act through a common site of action, but such site is highly stereospecific with regard to the neurosteroid spatial configuration.
Pignataro
L
L
Instituto de Biología Celular y Neurociencias Prof. Eduardo De Robertis, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, Argentina.
Fiszer de Plazas
S
S
D000818:Animals; D002645:Chickens; D004357:Drug Synergism; D005445:Flunitrazepam / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology*; D011277:Pregnanediones / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology*; D018079:Receptors, GABA / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium
D018755:GABA Agonists; D011277:Pregnanediones; D018079:Receptors, GABA; D014316:Tritium; D005445:Flunitrazepam; C006477:alphaxalone; D011280:Pregnanolone