Differential response of NADP-linked hepatic aldehyde dehydrogenase toward taurine: implication for behavioural effects of ethanol.
The effects of taurine, its initial precursor L-cysteine, and the major metabolite taurocholic acid on two ethanol-mediated responses in rodents were studied. Administration of a single dose of taurocholic acid reduced voluntary intake of a 5% ethanol solution by the rat. In the mouse, taurine had no effect on alcohol drinking or on the central depressant action of ethanol, as measured by the duration of ET-produced loss of the righting reflex. Likewise, taurocholic acid and L-cysteine did not significantly influence the duration of ethanol-narcosis time from control mice. Also studied were the effects of acute and short-term (7 or 10 days) administration of these compounds on hepatic ethanol and acetaldehyde metabolizing enzymes. Short-term administration of an equimolar concentration of taurine enhanced endogenous NADP-linked rat liver aldehyde dehydrogenase (L-ALDH) as contrasted with inhibition of the same enzyme by L-cysteine. Short-term (7 days) treatment with L-cysteine induced rat liver NAD-linked ALDH, but acute (single dose) treatment did not. Taurocholic acid short-term administration caused an induction and an inhibition of endogenous mouse liver alcohol dehydrogenase (L-ADH) and L-ALDH, respectively. The results suggest that taurine does not directly interact with ethanol. However, its major metabolite, taurocholic acid, may cause rapid metabolic conversion of ethanol to acetaldehyde by induction of L-ADH, which is then slowly metabolized due to a concomitant inhibition of L-ALDH. This may cause a build-up of acetaldehyde and thereby produce adverse reactions similar to those resulting from the combination of disulfiram and ethanol.
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003545:Cysteine / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013654:Taurine / Q000378:metabolism / Q000494:pharmacology*; D013656:Taurocholic Acid / Q000494:pharmacology
D013654:Taurine; D000431:Ethanol; D013656:Taurocholic Acid; D000444:Aldehyde Dehydrogenase; D003545:Cysteine