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Small molecule drug screening in Drosophila identifies the 5HT2A receptor as a feeding modulation target
Open accessAbstract
Dysregulation of eating behavior can lead to obesity, which affects 10% of the adult population worldwide and accounts for nearly 3 million deaths every year. Despite this burden on society, we currently lack effective pharmacological treatment options to regulate appetite. We used Drosophila melanogaster larvae to develop a high-throughput whole organism screen for drugs that modulate food intake. In a screen of 3630 small molecules, we identified the serotonin (5-hydroxytryptamine or 5-HT) receptor antagonist metitepine as a potent anorectic drug. Using cell-based assays we show that metitepine is an antagonist of all five Drosophila 5-HT receptors. We screened fly mutants for each of these receptors and found that serotonin receptor 5-HT2A is the sole molecular target for feeding inhibition by metitepine. These results highlight the conservation of molecular mechanisms controlling appetite and provide a method for unbiased whole-organism drug screens to identify novel drugs and molecular pathways modulating food intake.
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Metadata
- Authors
- Gasque, G., Conway, S., Huang, J., Rao, Y., & Vosshall, L. B.
- Venue
- Scientific Reports
- Published
- 2013-07-02
- Volume
- 3
- Issue
- 1
- Pages
- srep02120-srep02120
- ISSN
- 2045-2322 (ISSN-L)
- OpenAlex
- W2060870711
- Cited by
- 2,292
- References
- 41
- FWCI
- 118.83
- Type
- journal article
- Language
- en
- Open access
- gold
- Licence
- creativecommons.org/licenses/by-nc-sa/3.0/ (tdm)
- creativecommons.org/licenses/by-nc-sa/3.0/ (vor)
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