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Plasticity in serotonin control mechanisms in the gut
1Department of Anatomy and Cell Biology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA. mdg4@columbia.edu
Current Opinion in Pharmacology
|December 4, 2003
Summary
Serotonin transporter (SERT) is crucial for serotonin (5-HT) inactivation in the gut, expressed by enterocytes. The gut adapts to SERT inhibitors, allowing continued use of medications like SSRIs.
Area of Science:
- Neuroscience
- Gastroenterology
- Pharmacology
Background:
- 5-hydroxytryptamine (5-HT, serotonin) is vital for biological functions but requires membrane transport.
- Intracellular enzymes necessitate a high-affinity transporter, serotonin transporter (SERT), for 5-HT inactivation.
- SERT is in central/enteric neurons, but in the gut mucosa, enterocytes express SERT to manage 5-HT.
Purpose of the Study:
- To elucidate the role and localization of serotonin transporter (SERT) in the gastrointestinal mucosa.
- To understand the gut's adaptive mechanisms in response to SERT-inhibiting drugs.
Main Methods:
- This study focuses on the expression and function of SERT in enterocytes.
- Analysis of adaptive mechanisms in the gut following inhibition of SERT.
Main Results:
- SERT, not neuronal SERT, is the primary 5-HT transporter in the gastrointestinal mucosa.
- Inhibition of SERT by drugs like SSRIs and cocaine leads to adaptive changes in the gut.
- These adaptations involve backup transporters and altered receptor gene expression.
Conclusions:
- Enterocytes play a key role in regulating serotonin levels within the gastrointestinal tract via SERT.
- The gastrointestinal system exhibits resilience to SERT inhibition, mitigating severe toxicity through compensatory mechanisms.