Linked Life Data

19190238

Source:http://linkedlifedata.com/resource/pubmed/id/19190238

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-4-24
pubmed:abstractText
Proteinase-activated receptor (PAR)(2) is activated by trypsin-like serine proteinases and has been implicated in intestinal inflammation. However, its role in the regulation of intestinal mucosal function remains unclear. Using the intestinal epithelial cell line, SCBN, we have studied the stimulus-secretion coupling mechanisms of PAR(2)-induced epithelial chloride transport, focusing on cyclooxygenase (COX)-1 and COX-2 activities and prostaglandin (PG) E(2) secretion. SCBN monolayers were grown on Snapwell supports, mounted in modified Ussing chambers, and exposed to the activating peptide, SLIGRL-NH(2) (50 microM), to activate PAR(2). Pretreatment with inhibitors of cytosolic PLA(2) (cPLA(2)) (AACOCF3, arachidonyltrifluoromethyl ketone), COX-1 [SC560, 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole], and COX-2 (celecoxib) resulted in a significant concentration-dependent attenuation of PAR(2)-induced changes in short-circuit current. Immunoblot analysis showed a PAR(2)-induced increase in cPLA(2) phosphorylation that was blocked by the mitogen-activated protein kinase kinase inhibitor, PD98059 [2-(2-amino-3methoxyphenyl)-4H-1benzopyran-4-one, C(16)H(13)NO(3)], and the pan-protein kinase C inhibitor, GFX (bisindolylmaleimide). PAR(2) stimulation also resulted in a large increase in the production of PGE(2) as determined by enzyme-linked immunosorbent assay and was also blocked by PD98059 and GFX. Immunofluorescence and immunoblot analysis determined that EP2 and EP4 are expressed at the basolateral membrane of SCBN cells. Through the use of selective inhibitors (EP2, AH6809 [6-isopropoxy-9-oxoxanthene-2-carboxylic acid]; EP4, GW627368X [N-[2[4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl] acetyl]benzene sulphonamide]), it was found that both EP2 and EP4 were involved in mediating the PAR(2)-induced chloride secretory response. We conclude that basolateral PAR(2) activation induces epithelial chloride secretion that is mediated by cPLA(2), COX-1, COX-2, and the subsequent release of PGE(2). The production of PGE(2) results in an autocrine secretory response that is dependent on basolateral EP2 and EP4 receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
329
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
747-52
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19190238-Animals, pubmed-meshheading:19190238-Cell Line, pubmed-meshheading:19190238-Chlorine, pubmed-meshheading:19190238-Cyclooxygenase 1, pubmed-meshheading:19190238-Cyclooxygenase 2, pubmed-meshheading:19190238-Cyclooxygenase Inhibitors, pubmed-meshheading:19190238-Dinoprostone, pubmed-meshheading:19190238-Dogs, pubmed-meshheading:19190238-Dose-Response Relationship, Drug, pubmed-meshheading:19190238-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:19190238-Epithelial Cells, pubmed-meshheading:19190238-Immunoblotting, pubmed-meshheading:19190238-Intestinal Mucosa, pubmed-meshheading:19190238-Ion Transport, pubmed-meshheading:19190238-Receptor, PAR-2, pubmed-meshheading:19190238-Receptors, Prostaglandin E, pubmed-meshheading:19190238-Receptors, Prostaglandin E, EP2 Subtype, pubmed-meshheading:19190238-Receptors, Prostaglandin E, EP4 Subtype
pubmed:year
2009
pubmed:articleTitle
Prostaglandin E2 derived from cyclooxygenases 1 and 2 mediates intestinal epithelial ion transport stimulated by the activation of protease-activated receptor 2.
pubmed:affiliation
Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't