Possible Interaction: Gamma-Aminobutyric Acid and Dehydroepiandrosterone Sulfate

“The γ-aminobutyric acid type A receptor (GABAAR) is negatively modulated by two structurally similar neurosteroids, pregnenolone sulfate (PS) and dehydroepiandrosterone sulfate (DHEAS).”

“In vitro studies have demonstrated that DHEA-S , and perhaps DHEA, have GABA antagonistic activity.”

“BACKGROUND The neurosteroid dehydroepiandrosterone sulphate (DHEAS) activates the sigma-1 receptor, inhibits gamma-aminobutyric acid A (GABAA) and glycine receptors, and induces hyperalgesic effects.”

“ DHEAS suppressed the frequency of miniature inhibitory postsynaptic currents in a GABAA receptor- and sigma-1 receptor-dependent manner.”

“DHEA (100 μM) and DHEA-S (100 μM) also attenuated the effect of GABA.”

“Oocytes injected with the mutated gamma2 subunit showed no inhibition of GABA responses by picrotoxinin at concentrations up to 100 microM. PS and DHEAS inhibited GABA currents at similar concentrations in both sets of oocytes.”

“Furthermore, we confirmed that DHEAS inhibits GABA responses, as measured by GABA-induced [36Cl-] influx in cultured cortical neurons.”

“In contrast, DHEAS , but not DHEA, inhibited the binding of [3H]GABA and [35S]TBPS to rat brain cerebral cortical and cerebellar membranes in a concentration-dependent manner.”

“The results showed that the inhibitory effect of DHEAS (10(-6) M) on TNF production by THP-1 cells was completely reversed by addition of 10(-6) M GABA.”