Opposing effects of different steroid sulfates on GABAA receptor-mediated chloride uptake.
Steroids with the 3alpha-hydroxy-5alpha- or 5beta-reduced configurations of the A ring interact with the gamma-aminobutyric acid (GABA) type A receptor chloride channel complex and potentiate the stimulation of Cl- uptake by GABA agonists. Conversely, the sulfate esters of 3beta-hydroxy-5-ene neurosteroids pregnenolone and dehydroepiandrosterone behave as inhibitory modulators. In the present work, steroid sulfates were tested for their ability to modulate muscimol-induced chloride ion uptake into cortical synaptoneurosomes. 3alpha-Hydroxy-5alpha-pregnan-20-one sulfate and several other 3alpha-hydroxy-steroid sulfates potentiated, whereas 3beta-hydroxy-steroid sulfates inhibited muscimol effect. It is concluded that GABA-agonistic or antagonistic properties of steroid sulfates depend on the alpha or beta orientation of the sulfate moiety linked to the A ring.
El-Etr
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M
INSERM U.33, Lab. Hormones, 80 rue du Général Leclerc, 94276 Kremlin-Bicêtre, Cedex, France. eletr@kb.inserm.fr
Akwa
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Y
Robel
P
P
Baulieu
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EE
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D002712:Chlorides / Q000493:pharmacokinetics*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D002712:Chlorides; D018755:GABA Agonists; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D007476:Ionophores; D011963:Receptors, GABA-A; C018370:pregnenolone sulfate; D009118:Muscimol; D019314:Dehydroepiandrosterone Sulfate; D011284:Pregnenolone; D011280:Pregnanolone