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Defective cAMP‐dependent HCO3‐ Secretion Leads to Abnormal Mucus
Author(s) -
Yang Ning,
Garcia Mary Abigail S.,
Quinton Paul M.
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.608.13
Subject(s) - mucus , forskolin , secretion , goblet cell , intracellular , ibmx , endocrinology , cystic fibrosis , chemistry , medicine , biology , epithelium , biochemistry , stimulation , ecology , genetics
Cystic fibrosis (CF) is a hereditary, fatal disease caused by a unique pathology that appears to begin with thick mucus that obstructs the lumina of hollow organs. In the present study, PAS‐AB Staining, morphometry, pH stat and mucus collection assay methods were used to investigate the formation of abnormal mucus in CF mouse small intestine. We found that in the wild type mouse small intestine, carbachol (100 μM, an intracellular Ca 2+ mediated activator) induced goblet cell mucus release, but did not stimulate sustained HCO 3 − secretion. Whereas, forskolin (10 μM) + IBMX (100 μM) applied to activate intracellular cAMP‐mediated pathways did not have any detectable effect on goblet cell mucus release, but did induce sustained HCO 3 − secretion. With HCO 3 − in the basolateral solution, PGE 2 (1 μM) + 5‐HT (10 μM), cAMP and Ca 2+ mediated activators, induced more mucus release from goblet cells in the presence than in the absence of HCO 3 − . In CF mouse small intestine, PGE 2 (1 μM) + 5‐HT (10 μM) also stimulated goblet cell mucus release, but there was no significant difference in mucus releasing goblet cells with or without HCO 3 − in the basolateral solution. cAMP activated HCO 3 − secretion was missing in CF intestine. These results suggest that a defect in cAMP‐dependent HCO 3 − secretion, rather than in mucus release, leads to the abnormal mucus observed in CF mouse. Supported by Elizabeth Nash Memorial Fellowship