title: Epipregnanolone acts as a partial agonist on a common neurosteroid modulatory site of the GABA(A) receptor complex in avian CNS.
abstract: 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.
authors.affiliation: Instituto de Biología Celular y Neurociencias Prof. Eduardo De Robertis, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Pignataro
authors.forename: S
authors.initials: S
authors.lastname: Fiszer de Plazas
mesh_terms: 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
chemical_list: D018755:GABA Agonists; D011277:Pregnanediones; D018079:Receptors, GABA; D014316:Tritium; D005445:Flunitrazepam; C006477:alphaxalone; D011280:Pregnanolone