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Extracellular ATP synthesis regulates ATP release and bicarbonate secretion in rat duodenum
Author(s) -
Watanabe Chikako,
Akiba Yasutada,
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.799.9
Subject(s) - oligomycin , extracellular , atp synthase , v atpase , purinergic receptor , microbiology and biotechnology , biochemistry , p2 receptor , adenosine triphosphate , secretion , uridine diphosphate , atpase , chemistry , biology , enzyme
The pH of the alkaline microclimate overlying duodenal enterocyte brush border is regulated by an ecto‐purinergic signaling; intestinal alkaline phosphatase (IAP), extracellular ATP and P2Y receptors regulate duodenal bicarbonate secretion (DBS). IAP inhibition increases DBS and non‐lytic ATP release into the lumen by the mechanism unknown. Ecto‐F 1 F 0 ‐ATP synthase has been localized to plasma membranes of several cell types. We hypothesized that ecto‐ATP synthase generates extracellular ATP, regulating DBS. We measured DBS with flow‐through pH and CO 2 electrodes with perfusate ATP content measured by luciferin‐luciferase bioassay. We perfused the competitive AP inhibitor glycerol phosphate (GP) with ATP synthase inhibitors oligomycin (Om), piceatannol (Pic) or resveratorol (Res), or the uncoupler CCCP. GP increased DBS and ATP output. Pic or Res inhibited GP‐induced augmented DBS and ATP output. GP, Pic or Res with GP had no effect on LDH release, confirming no cellular injury. Om or CCCP inhibited GP‐induced ATP output with increased LDH release, consistent with cell injury. Luminal ATP release unmasked by IAP inhibition is dependent on ecto‐ATP synthase activity, consistent with the presence of ecto‐ATP synthase on the brush border. Ecto‐ATP synthesis and ATP degradation by IAP may coordinately regulate ATP‐P2Y signaling for DBS as part of a novel ecto‐purinergic signaling system. VA, NIH‐NIDDK