Linked Life Data

19535511

Source:http://linkedlifedata.com/resource/pubmed/id/19535511

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-9-7
pubmed:abstractText
Although phosphatidylinositol 3-kinase (PI3K) is essential for several cellular signal transductions, its role in the regulation of cystic fibrosis transmembrane conductance regulator (CFTR) activity in intestinal epithelial cells is poorly understood. Therefore, the possible involvement of PI3K in the regulation of cAMP- and cGMP-induced duodenal epithelial CFTR activation was investigated in the present study. Forskolin and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) markedly stimulated duodenal mucosal HCO(3)(-) secretion and short-circuit current (I(sc)) in CFTR wild-type mice, which was significantly inhibited by CFTR(inh)-172, a highly potent and specific CFTR inhibitor. Forskolin and 8-Br-cGMP failed to stimulate duodenal HCO(3)(-) secretion and I(sc) in CFTR knockout mice. Moreover, forskolin- and 8-Br-cGMP-stimulated duodenal HCO(3)(-) secretion and I(sc) were significantly reduced by wortmannin and LY294002, two selective PI3K inhibitors that are structurally and mechanistically different. Forskolin and 8-Br-cGMP induced CFTR phosphorylation and shifted CFTR proteins to the plasma membrane of duodenal epithelial cells, which were inhibited by wortmannin and LY294002. Forskolin and 8-Br-cGMP not only increased the activity of PI3K but also induced the phosphorylation of Akt, a signaling molecule downstream of PI3K, which were again inhibited by wortmannin and LY294002. Together, our results obtained from functional, biochemical, and morphological studies demonstrate that PI3K pathway plays an important role in the regulation of cAMP- and cGMP-induced duodenal epithelial CFTR channel activity and intracellular trafficking.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1522-1563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C503-15
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Involvement of phosphatidylinositol 3-kinase in cAMP- and cGMP-induced duodenal epithelial CFTR activation in mice.
pubmed:affiliation
Dept. of Gastroenterology, Affiliated Hospital of Zunyi Medical College, Dalian Road 149, Zunyi 563003, China. tuobiguang@yahoo.com.cn
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't