BACKGROUND & AIMS: 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. METHODS: 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. 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 [Ca(2+)](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.
BACKGROUND & AIMS: 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. METHODS: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. 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 [Ca(2+)](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.
Authors: A Chin; B Svejda; B I Gustafsson; A B Granlund; A K Sandvik; A Timberlake; B Sumpio; R Pfragner; I M Modlin; M Kidd Journal: Am J Physiol Gastrointest Liver Physiol Date: 2011-10-28 Impact factor: 4.052
Authors: A Kalhan; B Gharibi; M Vazquez; B Jasani; J Neal; M Kidd; I M Modlin; R Pfragner; D A Rees; J Ham Journal: Purinergic Signal Date: 2011-11-27 Impact factor: 3.765
Authors: Andrómeda Liñán-Rico; Jacqueline E Wunderlich; Iveta S Grants; Wendy L Frankel; Jianjing Xue; Kent C Williams; Alan E Harzman; Joshua T Enneking; Helen J Cooke; Fievos L Christofi Journal: Inflamm Bowel Dis Date: 2013-10 Impact factor: 5.325