title: Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model.
abstract: OBJECTIVE
  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.affiliation: Department of Anesthesiology, The Ohio State University, Columbus 43210, USA.
authors.forename: Fievos L
authors.initials: FL
authors.lastname: Christofi
authors.forename: Minsoo
authors.initials: M
authors.lastname: Kim
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Wunderlich
authors.forename: Jianjing
authors.initials: J
authors.lastname: Xue
authors.forename: Zach
authors.initials: Z
authors.lastname: Suntres
authors.forename: Arturo
authors.initials: A
authors.lastname: Cardounel
authors.forename: Najma H
authors.initials: NH
authors.lastname: Javed
authors.forename: Jun Ge
authors.initials: JG
authors.lastname: Yu
authors.forename: Iveta
authors.initials: I
authors.lastname: Grants
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Cooke
mesh_terms: D000241:Adenosine / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002276:Carcinoid Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D004759:Enterochromaffin Cells / Q000378:metabolism*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018047:Receptors, Purinergic P1; D012701:Serotonin; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium