Linked Life Data

8900131

Source:http://linkedlifedata.com/resource/pubmed/id/8900131

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
1996-12-16
pubmed:abstractText
Epidermal growth factor (EGF) and carbachol both inhibit calcium-activated chloride secretion by the human colonic epithelial cell line, T84. Although the inhibitory mechanism for the carbachol effect involves the 3,4,5,6-isomer of inositol tetrakisphosphate, the mechanisms responsible for the EGF effect have not yet been fully elucidated. Here, we studied the role of phosphatidylinositol 3-kinase (PI 3-kinase) in the inhibitory effect of EGF. The PI 3-kinase inhibitor, wortmannin, slightly increased basal chloride secretion and potentiated the secretory response to thapsigargin. Wortmannin also partially reversed EGF-induced, but not carbachol-induced, inhibition of thapsigargin-stimulated chloride secretion. Wortmannin alone had no effect on carbachol- or histamine-induced chloride secretion and completely reversed EGF-induced inhibition of the secretory response to these agonists. EGF, carbachol, histamine, and thapsigargin all increased levels of the 85-kDa regulatory subunit of PI 3-kinase in antiphosphotyrosine immunoprecipitates. However, only EGF significantly increased levels of the 110-kDa catalytic subunit. Furthermore, only EGF increased PI 3-kinase activity in an in vitro kinase assay. High levels of phosphatidylinositol (3)-monophosphate were present in unstimulated cells and significantly reduced by wortmannin. EGF, but not carbachol, rapidly increased levels of phosphatidylinositol (3,4)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate. Production of these lipids was also sensitive to wortmannin. Our data suggest that EGF activates PI 3-kinase and that its lipid products may mediate the inhibitory effect of EGF on calcium-dependent chloride secretion. Our data also suggest that a phosphatidylinositol-specific 3-kinase activity is present in unstimulated T84 cells and may regulate production of phosphatidylinositol (3)-monophosphate and basal secretory tone.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26588-95
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Phosphatidylinositol 3-kinase mediates the inhibitory effect of epidermal growth factor on calcium-dependent chloride secretion.
pubmed:affiliation
Department of Medicine, University of California, San Diego, School of Medicine, San Diego, California 92103, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.