Linked Life Data

8572219

Source:http://linkedlifedata.com/resource/pubmed/id/8572219

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6 Pt 1
pubmed:dateCreated
1996-3-7
pubmed:abstractText
The involvement of tyrosine phosphorylation in the regulation of epithelial cell Cl- secretion is unknown. Therefore, the purpose of these studies was to determine if tyrosine kinase activation was involved in the regulation of Cl- secretion, using the tyrosine kinase inhibitors, genistein and tyrphostin 47, and human intestinal epithelial cells (T84 cells) as an intestinal Cl- secretory model. Genistein rapidly but reversibly stimulated sustained apical Cl- secretion in monolayers of T84 cells without increasing intracellular cyclic nucleotides or Ca2+ levels. Tyrphostin 47 also stimulated Cl- secretion in T84 monolayers, although it was short-lived. Transfection experiments in 3T3 fibroblasts and IEC-6 intestinal cells utilizing wild-type cystic fibrosis transmembrane conductance regulator (CFTR) showed that genistein and tyrphostin 47 stimulated 125I efflux only in CFTR-transfected cells and not in CFTR-negative cells. Thus genistein- and tyrphostin 47-stimulated Cl- secretion involved CFTR. Genistein also acted synergistically with the Ca(2+)- and protein kinase C-dependent acetylcholine analogue, carbachol, to stimulate Cl- secretion in T84 monolayers. However, the Cl- secretory response to saturating concentrations of the adenosine 3',5'-cyclic monophosphate (cAMP) agonist, forskolin, or the guanosine 3',5'-cyclic monophosphate (cGMP) agonist, Escherichia coli heat-stable enterotoxin, was not further enhanced by genistein. Although the mechanism of activation of Cl- secretion is unclear, these data suggest that tyrosine kinase activity limits basal Cl- secretion in T84 cells and that inhibition of T84 cell tyrosine kinase(s) stimulates apical membrane Cl- secretion, most likely through activation of the CFTR-Cl- channel. Moreover, genistein does not itself act through cAMP or cGMP elevation but appears to share a common Cl- secretory pathway with cyclic nucleotide-dependent agonists, whereas it augments the secretory responses to a Ca(2+)- and protein kinase C-dependent agonist.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CFTR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Chloride Channels, http://linkedlifedata.com/resource/pubmed/chemical/Chlorides, http://linkedlifedata.com/resource/pubmed/chemical/Cystic Fibrosis Transmembrane..., http://linkedlifedata.com/resource/pubmed/chemical/Genistein, http://linkedlifedata.com/resource/pubmed/chemical/Isoflavones, http://linkedlifedata.com/resource/pubmed/chemical/Nitriles, http://linkedlifedata.com/resource/pubmed/chemical/Nucleotides, Cyclic, http://linkedlifedata.com/resource/pubmed/chemical/Phenols, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins, http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin 47
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G874-82
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Genistein and tyrphostin 47 stimulate CFTR-mediated Cl- secretion in T84 cell monolayers.
pubmed:affiliation
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't