Naslov
Modulation of recombinant GABA-A receptors by neurosteroid dehydroepiandrosterone sulphate

Autori
Švob Štrac, Dubravka ; Jazvinšćak Jembrek, Maja ; Erhardt, Julija ; Mirković Kos, Kety ; Peričić, Danka

Izvornik
Pharmacology (0031-7012) 89 (2012), 3/4; 163-171

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
DHEAS; GABA-A receptor; HEK 293 cells; long-term treatment; ligand binding

Sažetak
Aim was to investigate whether long-term exposure to neurosteroid dehydroepiandrosterone sulfate (DHEAS) induces adaptive changes of GABA-A receptors related to the development of tolerance and dependence. We compared the parameters of [3H]DHEAS binding and the effects of DHEAS on [3H]flunitrazepam binding in the membranes of HEK 293 cells, nontransfected or stably transfected with recombinant α1β2γ2S GABA-A receptors. In HEK 293 cells expressing α1β2γ2S GABA-A receptors we investigated the effects of long-term DHEAS treatment on the [3H]flunitrazepam and [3H]TBOB binding and on their modulation with GABA. DHEAS behaves as an allosteric antagonist of the recombinant α1β2γ2S GABA-A receptors expressed in HEK 293 cells. Exposure of cells to 100 microM DHEAS for 48 h have not changed the number or affinity of benzodiazepine and convulsive binding sites. Long-term DHEAS treatment failed to affect functional allosteric interactions between GABA-A receptor binding sites, as evidenced by a unchanged ability of GABA to stimulate or to inhibit [3H]flunitrazepam and [3H]TBOB binding, respectively. The findings that prolonged DHEAS treatment does not produce changes in GABA-A receptor expression and functional coupling, assumed to underlie the development of tolerance and dependence, might have importance in the long- term therapy necessary for the observed beneficial effects of DHEAS.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA