Linked Life Data

11447011

Source:http://linkedlifedata.com/resource/pubmed/id/11447011

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-7-11
pubmed:abstractText
The thrombin receptor, protease-activated receptor-1 (PAR-1), has wide tissue distribution and is involved in many physiological functions. Because thrombin is in the intestinal lumen and mucosa during inflammation, we sought to determine PAR-1 expression and function in human intestinal epithelial cells. RT-PCR showed PAR-1 mRNA expression in SCBN cells, a nontransformed duodenal epithelial cell line. Confluent SCBN monolayers mounted in Ussing chambers responded to PAR-1 activation with a Cl(-)-dependent increase in short-circuit current. The secretory effect was blocked by BaCl2 and the Ca(2+)-ATPase inhibitor thapsigargin, but not by the L-type Ca(2+) channel blocker verapamil or DIDS, the nonselective inhibitor of Ca(2+)-dependent Cl(-) transport. Responses to thrombin and PAR-1-activating peptides exhibited auto- and crossdesensitization. Fura 2-loaded SCBN cells had increased fluorescence after PAR-1 activation, indicating increased intracellular Ca(2+). RT-PCR showed that SCBN cells expressed mRNA for the cystic fibrosis transmembrane conductance regulator (CFTR) and hypotonicity-activated Cl(-) channel-2 but not for the Ca(2+)-dependent Cl(-) channel-1. PAR-1 activation failed to increase intracellular cAMP, suggesting that the CFTR channel is not involved in the Cl(-) secretory response. Our data demonstrate that PAR-1 is expressed on human intestinal epithelial cells and regulates a novel Ca(2+)-dependent Cl(-) secretory pathway. This may be of clinical significance in inflammatory intestinal diseases with elevated thrombin levels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G323-32
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Protease-activated receptor-1 stimulates Ca(2+)-dependent Cl(-) secretion in human intestinal epithelial cells.
pubmed:affiliation
Mucosal Inflammation Research Group, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't