Studies on the interaction between ethanol and serotonin metabolism in rat, using deuterated ethanol and 4-methylpyrazole

The metabolic interaction between ethanol and serotonin (5-hydroxytryptamin e) via alcohol dehydrogenase (ADH; EC 1.1.1.1) was studied in tissue homoge nates of Sprague-Dawley rats by following the transfer of deuterium from de uterated ethanol over endogenous NADH to 5-hydroxytryptophol (5HTOL). Homog enates of whole brain, lung, spleen, kidney, liver, stomach, jejunum, ileum , colon, and caecum were incubated in the presence of [H-2(2)]ethanol and 5 -hydroxyindole-3-acetaldehyde (5HIAL), and the [H-2]5HTOL formed was identi fied and quantified using gas chromatography-mass spectrometry. ADH activit y was most abundant in liver, kidney, and within the gastrointestinal tract . The highest incorporation of deuterium was obtained in homogenates of kid ney, lung, and colon, whereas in brain, which contains very low ADH activit y, no incorporation could be demonstrated. Addition of extra NAD(+) (2.4 mM ) increased the formation of [H-2]5HTOL 2.6-fold in liver homogenates, but only 1.2-fold in kidney homogenates. 4-Methylpyrazole, a potent inhibitor o f class I ADH, inhibited the 5HIAL reduction in homogenates of lung, kidney , jejunum, ileum, and colon, and caused a marked drop in 5HTOL oxidation in all tissues except stomach and spleen. These results demonstrate that in t he rat a metabolic interaction between ethanol and serotonin via the ADH pa thway may take place in several tissues besides the liver, which is the mai n tissue for ethanol detoxification. BIOCHEM PHARMACOL 59;4:385-391, 2000. (C) 2000 Elsevier Science Inc.