The neurosteroid dehydroepiandrosterone sulfate is an allosteric antagonist of the GABAA receptor.
Binding of the neurosteroid dehydroepiandrosterone sulfate (DHEAS) to rat brain synaptosomal membranes was studied in vitro, and the interaction of DHEAS with the GABAA receptor was tested using biochemical and electrophysiological assays. DHEAS bound to two populations of sites, and its binding was inhibited by barbiturates. DHEAS interfered with barbiturate-mediated enhancement of benzodiazepine binding. In cultured neurons from ventral mesencephalon, DHEAS reversibly blocked GABA-induced currents, behaving as an allosteric antagonist of the GABAA receptor.
Majewska
M D
MD
Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.
Demirgören
S
S
Spivak
C E
CE
London
E D
ED
D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013256:Steroids / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects
D058787:GABA-A Receptor Antagonists; D013256:Steroids; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate