Decreased cerebral cortex and liver 5-HT2A receptor gene expression and enhanced ALDH activity in ethanol-treated rats and hepatocyte cultures
| Autor: | Akash K. George, Sankara Balarama Kaimal, Jes Paul, C.S. Paulose |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Aging Serotonin Ketanserin medicine.drug_class Gene Expression Biology chemistry.chemical_compound Internal medicine medicine Animals Receptor Serotonin 5-HT2A RNA Messenger Rats Wistar Receptor Cells Cultured Cerebral Cortex Ethanol Central Nervous System Depressants General Medicine Aldehyde Dehydrogenase Receptor antagonist Rats medicine.anatomical_structure Endocrinology Neurology chemistry Liver Cerebral cortex Hepatocyte Hepatocytes Aldh activity Neurology (clinical) medicine.drug |
| Zdroj: | Neurological research. 32(5) |
| ISSN: | 1743-1328 |
| Popis: | 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.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).Decreased 5-HT content (p0.05 and p0.001) and decreased (p0.001) 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 (p0.001), and it decreased (p0.001) 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.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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|