Paulose, C S; Akash, K George; Anju, T R(Springer Science+Business Media, LLC 2009, February 24, 2009)
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Abstract:
Brain serotonin (5-HT) modulates the neural
effects of ethanol. In the present study, we investigated the
changes in 5-HT level, 5-HT2A receptor binding and aldehyde
dehydrogenase (ALDH) activity in brain stem and
liver of ethanol treated rats and 5-HT2A regulation on ALDH
in hepatocyte cultures in vitro. The 5-HT content in the brain
stem and liver significantly decreased with an increased
5-HIAA/5-HT ratio in the ethanol treated rats compared to
control. Scatchard analysis of [3H] (±)2,3-dimethoxyphenyl-
1-[2-(-4-piperidine)-methanol] [3H] MDL 100907
against ketanserin in brain stem of ethanol treated rats
showed a significant increase in Bmax without any change in
Kd compared to control. The competition curve for [3H]
MDL 100907 against ketanserin fitted one-site model in
both control and ethanol treated rats with unity as Hill slope
value. A significant increase in Vmax of ALDH activity in
liver and a significant decrease in Km in liver and brain stem
of ethanol treated rats compared to control was observed. In
24 h culture studies, an increase in enzyme activity was
observed in cells in medium with 10% ethanol. The elevated
ALDH activity in ethanol treated cells was reversed
to control level in presence of 10-5 and 10-7 M 5-HT.
Ketanserin, an antagonist of 5-HT2A, reversed the effect of
5HT on 10%ethanol induced ALDH activity in hepatocytes.
Our results showed that there was a decreased 5-HT content
with an enhanced 5-HT2A receptor and aldehyde dehydrogenase
activity in the brain stem of alcohol treated rats and
in vitro hepatocyte cultures. The enhanced ALDH activity in ethanol supplemented hepatocytes was reversed to control
level in presence of 10-5 and 10-7 M 5-HT.