A rapid new assay to detect RNA editing reveals antipsychotic-induced changes in serotonin-2C transcripts.
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Sodhi MS, Airey DC, Lambert W, Burnet PW, Harrison PJ, Sanders-Bush E
A rapid new assay to detect RNA editing reveals antipsychotic-induced changes in serotonin-2C transcripts.
Mol Pharmacol. 2005 Sep;68(3):711-9. Epub 2005 May 25.
- PubMed ID
- 15917433 [ View in PubMed]
- Abstract
We report the development of a new assay as an alternative to direct DNA sequencing to measure RNA-edited variation in tissue. The new assay has been validated and is accurate, cheaper, more rapid, and less labor-intensive than DNA sequencing. We also outline the statistical modeling required for analyses of the hierarchical, clustered RNA-editing data generated in these studies. Using the new technique, we analyzed the effects of long-term antipsychotic medication on serotonin-2C receptor (5-HT2CR) RNA editing in rat brain. Our hypothesis that a drug with high affinity for 5-HT2CR, such as clozapine, would alter its RNA-editing profile was not confirmed. Whereas haloperidol, a typical antipsychotic drug that is primarily a dopamine receptor antagonist, reduced 5-HT2C VNV isoform frequency and the level of RNA editing at the D site, risperidone and not the prototype atypical antipsychotic drug clozapine increased the frequency of 5-HT2C VNV and D-site editing. Our data emphasize that caution is required in the interpretation of RNA-editing data in studies of psychiatric disorders, because these studies usually include subjects who received long-term exposure to medication. This newly established method will facilitate high-throughput investigations of RNA editing in disease pathology and in the pharmacological activity of drugs.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Clozapine 5-hydroxytryptamine receptor 2C Protein Humans UnknownAntagonistDetails