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Luminal ATP release is impaired in intestinal alkaline phosphatase knockout mice duodenum
Author(s) -
Akiba Yasutada,
Watanabe Chikako,
Nakano Takanari,
Narisawa Sonoko,
Millan Jose Luis,
Kaunitz Jonathan D
Publication year - 2010
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.24.1_supplement.1004.1
Subject(s) - duodenum , cystic fibrosis transmembrane conductance regulator , alkaline phosphatase , knockout mouse , endocrinology , medicine , nucleoside triphosphate , multidrug resistance associated protein 2 , adenosine triphosphate , chemistry , brush border , adenosine , biology , atp binding cassette transporter , biochemistry , receptor , nucleotide , enzyme , transporter , cystic fibrosis , vesicle , membrane , gene
Brush border intestinal alkaline phosphatase (IAP) pH‐dependently regulates the concentration of luminally‐released ATP, which stimulates duodenal bicarbonate secretion (DBS) via P2Y receptors. We hypothesized that lack of IAP increases luminal [ATP], enhancing DBS. We measured DBS with pH and CO 2 electrodes and ATP with luciferin‐luciferase in a perfused duodenal loop in wild type (WT) or knockout (KO) mice lacking Akp3 (duodenal IAP equivalent) expression, or in SD rats. ATP degradation was impaired in KO duodenum, consistent with the role of IAP in ATP degradation. AP inhibition with glycerol phosphate (GP) increased DBS, inhibited by the P2 receptor antagonist suramin, with increased luminal [ATP] in WT mice and rat duodenum. In contrast, GP or suramin had no effect on DBS and ATP release in KO duodenum. Real‐time PCR revealed that the expression of multidrug resistant‐associate protein 2 (MRP2) was selectively downregulated with no change in the expression of other MRPs, multidrug resistance protein (MDR) 1a, ecto‐nucleoside triphosphate diphosphohydrolase isozymes or cystic fibrosis transmembrane conductance regulator. Furthermore, the MRP inhibitor MK571 inhibited GP‐induced ATP release in rat duodenum. These results suggest that lack of IAP impairs ATP release via downregulation of MRP2, which may participate in the epithelial ATP release. NIH‐NIDDK R01 DK54221