RGD Reference Report - Decreased cerebral cortex and liver 5-HT2A receptor gene expression and enhanced ALDH activity in ethanol-treated rats and hepatocyte cultures. - Rat Genome Database

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Decreased cerebral cortex and liver 5-HT2A receptor gene expression and enhanced ALDH activity in ethanol-treated rats and hepatocyte cultures.

Authors: George, Akash K  Paul, Jes  Kaimal, Sankara B  Paulose, C S 
Citation: George AK, etal., Neurol Res. 2010 Jun;32(5):510-8. doi: 10.1179/174313209X385554.
RGD ID: 401900301
Pubmed: PMID:20501057   (View Abstract at PubMed)
DOI: DOI:10.1179/174313209X385554   (Journal Full-text)


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.
CONCLUSION: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
alcohol use disorder  ISOHtr2a (Rattus norvegicus)401900301; 401900301mRNA more ...RGD 
alcohol use disorder  IEP 401900301mRNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Htr2a  (5-hydroxytryptamine receptor 2A)

Genes (Mus musculus)
Htr2a  (5-hydroxytryptamine (serotonin) receptor 2A)

Genes (Homo sapiens)
HTR2A  (5-hydroxytryptamine receptor 2A)


Additional Information