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

Gastroenterology
Fievos L ChristofiHelen J Cooke

Abstract

The aim was to determine whether adenosine receptors modulate cAMP, intracellular free calcium ([Ca(2+)](i)), and 5-hydroxytryptamine (5-HT) release in human carcinoid BON cells. Adenosine receptor (R) mRNA, proteins, and function were identified by Western blots, immunofluorescent labeling, Fluo-4/AM [Ca(2+)](i) imaging, and pharmacologic/physiologic techniques. 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 [Ca(2+)](i) responses were augmented by adenosine deaminase, A1, and A3R antagonists. 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.

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Citations

Jul 8, 2008·Purinergic Signalling·Fievos Leontiou Christofi
Nov 1, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·A ChinM Kidd
Oct 8, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Andrey BozarovFievos L Christofi
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Jul 29, 2017·Frontiers in Pharmacology·Andromeda Liñán-RicoFievos L Christofi

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