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Published on: September 23, 2015
A 5-HT2 receptor mediates serotonin-induced electrolyte transport in rat left colon
1Division of General & Trauma Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23284.
Abstract:
Serotonin (5-hydroxytryptamine, 5-HT) is a potent mediator of diarrhea in the carcinoid syndrome. However, the mechanisms of serotonin-induced intestinal secretion remain unclear. The purpose of this study was to determine whether 5-HT stimulates electrolyte transport by a direct action at a mucosal receptor. Serotonin-stimulated electrolyte transport was studied in flat sheet preparations of rat left colon using flux chambers. 5-HT stimulated a concentration-dependent rise in short-circuit current in sheets stripped of muscularis propria. The half-maximal concentration required to produce this effect was 50 microM. The preferential 5-HT2 antagonist ketanserin produced a rightward shift of the serotonin concentration-response curve with a pA2 value of 7.7. Serotonin stimulated electrolyte transport by inhibiting mucosa to serosa movement of both sodium and chloride. The 5-HT1 antagonist N-acetyl-5-hydroxytryptophyl 5-hydroxytryptophan amide and the 5-HT3 antagonist 3-tropanyl-indole-3-carboxylate methiodide had no effect on these actions of serotonin on electrolyte transport. In contrast, ketanserin inhibited the actions of serotonin on both sodium and chloride movement and inhibited the rise in short-circuit current induced by 100 microM 5-HT. This study demonstrates that a 5-HT2 receptor located in the vicinity of the mucosa is involved in the regulation of serotonin-stimulated intestinal electrolyte transport.
Insights
Serotonin (5-hydroxytryptamine, 5-HT) triggers intestinal secretion by acting on a specific mucosal receptor. This research identifies the 5-HT2 receptor as key in mediating serotonin
Area of Science:
- Gastroenterology
- Pharmacology
- Molecular Biology
Background:
- Serotonin (5-hydroxytryptamine, 5-HT) is a key mediator of diarrhea in carcinoid syndrome.
- The precise mechanisms underlying serotonin-induced intestinal secretion are not fully understood.
Purpose of the Study:
- To investigate if serotonin stimulates electrolyte transport via direct action on mucosal receptors.
- To elucidate the specific serotonin receptor subtype involved in intestinal secretion.
Main Methods:
- Utilized rat left colon flat sheet preparations in flux chambers to study serotonin-induced electrolyte transport.
- Measured short-circuit current and ion movement (sodium and chloride) in response to serotonin.
- Employed selective serotonin receptor antagonists (ketanserin for 5-HT2, and others for 5-HT1 and 5-HT3) to identify receptor involvement.
Main Results:
- Serotonin induced a concentration-dependent increase in short-circuit current, indicating stimulated electrolyte transport.
- The 5-HT2 antagonist ketanserin significantly inhibited serotonin's effect on electrolyte transport, with a pA2 value of 7.7.
- Serotonin's action involved inhibiting both sodium and chloride movement from mucosa to serosa.
- 5-HT1 and 5-HT3 antagonists did not affect serotonin-induced electrolyte transport.
Conclusions:
- A 5-HT2 receptor located near the colonic mucosa plays a crucial role in regulating serotonin-stimulated intestinal electrolyte transport.
- This finding provides insight into the pathophysiology of carcinoid syndrome-related diarrhea and potential therapeutic targets.
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