Effects of the androgenic/anabolic steroid stanozolol on GABAA receptor function: GABA-stimulated 36Cl- influx and [35S] TBPS binding.
We have recently demonstrated that androgenic/anabolic steroids modulate in vitro ligand binding to the benzodiazepine binding site(s) associated with the gamma-aminobutyric acidA (GABAA) receptor complex (Masonis and McCarthy, 1995). One androgenic/anabolic steroid in particular, stanozolol, appears to stabilize the GABAA receptor in a moderate-affinity state for benzodiazepine binding. In the present study, we demonstrate the effects of stanozolol on the functional responsiveness of the GABAA receptor. After pre-incubation with stanozolol, we observed a decrease in the Emax and EC50 values for GABA-stimulated 36Cl- influx into cortical synaptoneurosomes. Moreover, in the presence of stanozolol, flunitrazepam-enhanced GABA-stimulated 36Cl- influx was lost, and the GABAA receptor was stabilized in a functional state that was resistant to further desensitization by agonist. Stanozolol does not appear to reduce GABA-stimulated 36Cl- influx by acting as a channel blocker at the well-characterized channel blocker binding site, as illustrated by the GABA-sensitive biphasic effects of stanozolol on [35S] t-butylbicyclophosphorothionate binding. These results demonstrate a novel, nongenomic mechanism for androgenic/anabolic steroidal modulation of CNS function.
Masonis
A E
AE
Dept. of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway.
McCarthy
M P
MP
D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D013197:Stanozolol / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D045930:Anabolic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002712:Chlorides; D011963:Receptors, GABA-A; D013197:Stanozolol; D005680:gamma-Aminobutyric Acid; C037476:tert-butylbicyclophosphorothionate