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Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model
Fievos L Christofi1, Minsoo Kim, Jacqueline E Wunderlich
1Department of Anesthesiology, The Ohio State University, Columbus 43210, USA.
Adenosine receptors influence serotonin release in carcinoid cells. Endogenous adenosine release is key for gut mechanosensory reflexes, impacting serotonin (5-HT) levels and calcium signaling.
Area of Science:
- Gastroenterology
- Neuroscience
- Cellular Biology
Background:
- Human carcinoid BON cells and tumors express adenosine receptors.
- Adenosine signaling plays a role in cellular functions within the gut.
Purpose of the Study:
- To investigate the role of adenosine receptors in modulating cAMP, intracellular calcium ([Ca(2+)](i)), and serotonin (5-HT) release in human carcinoid BON cells.
- To understand the impact of adenosine receptor activation and blockade on 5-HT release and calcium signaling.
Main Methods:
- Adenosine receptor (R) mRNA, proteins, and function were analyzed using Western blots and immunofluorescent labeling.
- Intracellular calcium ([Ca(2+)](i)) imaging was performed using Fluo-4/AM.
- Pharmacologic and physiologic techniques were employed to assess receptor function and 5-HT release.
Main Results:
- A1, A2, and A3 adenosine receptors were detected in BON cells and carcinoid tumors.
- Adenosine deaminase, A2R activation, and A3R inhibition increased baseline 5-HT, while A3R activation decreased it.
- A2R antagonists or blockade of adenosine reuptake reduced mechanically evoked 5-HT release; touch-evoked [Ca(2+)](i) responses were augmented by adenosine deaminase and A1/A3R antagonists.
Conclusions:
- Tonic and mechanically evoked release of endogenous adenosine are critical for differential adenosine receptor activation.
- Adenosine receptor modulation of 5-HT release and calcium signaling has significant implications for gut mechanosensory reflexes.
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