Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model

Background & Aims: The aim was to determine whether adenosine receptors modulate CAMP, intracellular free calcium ([Ca2+](i)), and 5-hydroxytrypta mine (5-HT) release in human carcinoid BON cells. Methods: Adenosine receptor (R) mRNA, proteins, and function were identified by Western blots, immunofluorescent labeling, Fluo-4/AM [Ca2+](i) imaging, and pharmacologic/ physiologic techniques. Results: A1, A2, and A3Rs were present in BON cells and carcinoid tumors. Baseline 5-HT levels increased with adenosine deaminase, activation of A2Rs, and inhibition of A3Rs, whereas A3R activation decreased 5-HT. A2R antagonists or blockade of adenosine reuptake that elevates extracellular adenosine reduced mechanically evoked 5-HT release. In single BON cells, touch elevated [Ca2+](i) responses were augmented by adenosine deaminase, A1, and A3R antagonists. Conclusions: Tonic or mechanically evoked release of endogenous adenosine is a critical determinant of differential activation of adenosine receptors and may have important implications for gut mechanosensory reflexes.