Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model.
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.
Christofi
Fievos L
FL
Department of Anesthesiology, The Ohio State University, Columbus 43210, USA.
Kim
Minsoo
M
Wunderlich
Jacqueline E
JE
Xue
Jianjing
J
Suntres
Zach
Z
Cardounel
Arturo
A
Javed
Najma H
NH
Yu
Jun Ge
JG
Grants
Iveta
I
Cooke
Helen J
HJ
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
D018047:Receptors, Purinergic P1; D012701:Serotonin; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium