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Luminal adenosine signaling regulates duodenal bicarbonate secretion via A 2B receptor and CFTR in rats
Author(s) -
Akiba Yasutada,
Ham Maggie,
Watanabe Chikako,
Nakano Takanari,
Kaunitz Jonathan D
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.799.8
Subject(s) - adenosine , endocrinology , medicine , agonist , chemistry , pharmacology , receptor , biology
Duodenal bicarbonate secretion (DBS) is increased by luminal ATP, via activation of enterocyte brush border P2Y 1 receptors. Increased DBS augments the activity of intestinal alkaline phosphatase (IAP) activity, which degrades luminal ATP, acting as a negative feedback loop. Since IAP dephosphorylates ATP to ADP, AMP, and adenosine (ADO), and since adenosine deaminase (ADA) is highly expressed in duodenal brush border, we hypothesized that luminal ADO signaling is also involved in DBS regulation. We measured DBS with flow‐through pH and CO 2 electrodes, testing the effect of perfusion of ATP, ADP, AMP or ADO with or without adenosine receptor (A 1‐3 R) agonists or antagonists, or CFTR inhibitor CFTR inh ‐172 on DBS. We also examined the effect of inhibitors of ADA or concentrative nucleoside transporter (CNT) on DBS. Perfusion of ATP, ADP, AMP or ADO uniformly increased DBS. A 2B R agonist NECA increased DBS, whereas ADO‐augmented DBS was inhibited by A 2B R antagonist MRS1754 and abolished by CFTR inh ‐172. Other AR agonists or antagonists had no effect. A 2B R was immunolocalized to the brush border of duodenal villi whereas A 2A R to the endothelium. ADA inhibitor EHNA and CNT inhibitor formycin B enhanced ADO‐induced DBS. Luminal ADO stimulates DBS via A 2B R and CFTR. IAP, ADA and CNT may coordinately regulate luminal ADO concentration to modulate ADO‐P1R signaling in rat duodenum. VA Merit Review, NIH‐NIDDK R01 DK54221