Allosteric modulation of α1β3γ2 GABA_A receptors by farnesol through the neurosteroid sites.

ABSTRACT: In mammalian cells, all-trans farnesol, a 15-carbon isoprenol, is a product of the mevalonate pathway. It is the natural substrate of alcohol dehydrogenase and a substrate for CYP2E1, two enzymes implicated in ethanol metabolism. Studies have shown that farnesol is present in the human brain and inhibits voltage-gated Ca²⁺ channels at much lower concentrations than ethanol. Here we show that farnesol modulates the activity of γ-aminobutyric acid type A receptors (GABA_ARs), some of which also mediate the sedative activity of ethanol. Electrophysiology experiments performed in HEK cells expressing human α1β3γ2 or α6β3γ2 GABA_ARs revealed that farnesol increased chloride currents through positive allosteric modulation of these receptors and showed dependence on

SUBMITTER: Gc JB 

PROVIDER: S-EPMC10027449 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature