Decreased cerebral cortex and liver 5-HT2A receptor gene expression and enhanced ALDH activity in ethanol-treated rats and hepatocyte cultures.
OBJECTIVE
In this work, we evaluated the differential binding of serotonin 2A (5-HT(2A)) receptor antagonist [(3)H](+/-)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] ([(3)H] MDL 100907) to 5-HT(2A) receptors in cerebral cortex and liver.


METHODS
Wistar adult male rats of 180-200 g body weight were given free access to 15% (v/v; approximately 7.5 g/kg body weight per day) ethanol for 15 days. Brain 5-HT and its metabolites were assayed by a high-performance liquid chromatography. 5-HT(2A) receptor binding assay was done with different concentrations of [(3)H] MDL 100907. Hepatocyte culture was done with 10(-9)-10(-3)M of 5-HT and ketanserin. The hepatocytes were incubated for 24 hours at 37 degrees C in 5% CO(2).


RESULTS
Decreased 5-HT content (p<0.05 and p<0.001) and decreased (p<0.001) 5-HT(2A) receptor binding in cerebral cortex and liver of ethanol-treated rats were observed when compared with control. 5-HT(2A) receptor mRNA in the cerebral cortex and liver showed an increase in crossing threshold value showing decrease in gene expression in ethanol-treated rats when compared with control. In 24-hour culture works, hepatocytes with 10% ethanol showed an increase in aldehyde dehydrogenase (ALDH) activity (p<0.001), and it decreased (p<0.001) to a near-control level in the case of hepatocytes in a medium with 10% ethanol + 10(-5)M 5-HT and 10% ethanol + 10(-7)M 5-HT when compared with the hepatocytes in the medium with 10% ethanol.


CONCLUSIONS
Our results suggest that the decreased serotonin function mediated through 5-HT(2A) receptors have a regulatory role on ALDH activity. This will have clinical significance to correct alcoholics from addiction due to allergic aldehyde accumulation.
George
Akash K
AK
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, India.
Paul
Jes
J
Kaimal
Sankara B
SB
Paulose
C S
CS
D000375:Aging; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
D002492:Central Nervous System Depressants; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; D000431:Ethanol; D000444:Aldehyde Dehydrogenase