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CFTR‐dependent HCO3‐ defect, cause of viscous mucus in distal intestinal obstruction syndrome (DIOS)?
Author(s) -
Yang Ning,
Quinton Paul M.
Publication year - 2012
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.26.1_supplement.695.1
Subject(s) - mucus , ileum , cystic fibrosis , chemistry , medicine , secretion , ussing chamber , small intestine , endocrinology , biology , biochemistry , ecology
Background & Aim Distal intestinal obstruction syndrome (DIOS) is a condition unique to Cystic Fibrosis, which is due to the accumulation of abnormally viscous mucus in the intestinal tract. However, the pathogenesis of DIOS has not been determined. This study is to test our hypothesis that the CFTR‐dependent HCO 3 − defect is a cause of more viscous mucus in DIOS. Methods Segments of distal small intestine (ileum) and distal colon from CL57B1/6 WT mice were incubated with stimulants in vitro in either NaCl (no HCO 3 − ) or NaHCO 3 (with HCO 3 − ) Ringers solution. Mucus samples were collected from the incubated intestines and analyzed by a spot tracking method for mucus viscosity. pH‐stat and Ussing chamber techniques were used to measure HCO 3 − secretion. Results After stimulating with 5‐HT (10 μM) and PGE2 (1 μM), we found that the mucus viscosity from both ileal and distal colonic sacs incubated with HCO 3 − Ringer solution was significantly lower than the mucus from sacs incubated in Ringer solution without HCO 3 − , indicating that HCO 3 − secretion decreased the mucus viscosity in both the mouse ileum and distal colon. However, we found that CFTR inhibitor, glyH‐101 (20 μM) significantly inhibited 5‐HT and PGE2‐induced HCO 3 − secretion only in the ileum, not in the distal colon, suggesting that HCO 3 − secretion in the ileum is CFTR‐dependent. Summary The CFTR‐dependent HCO 3 − defect in the distal small intestine is probably a cause of the more viscous mucus in DIOS.