Document Detail

Protease-activated receptor-2 regulates bicarbonate secretion by pancreatic duct cells in vitro.
MedLine Citation:
PMID:  15349117     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Pancreatic duct cells (PDCs) are responsible for bicarbonate production by the pancreas. The trypsin-sensitive protease-activated receptor (PAR-2), also known as the trypsin receptor, is highly expressed in the pancreatic duct system and has been shown to regulate PDC ion transport. The possible role of this receptor on bicarbonate secretion, the central function of duct cells, is unknown. We hypothesize that PAR-2 may regulate pancreatic bicarbonate secretion during times of inappropriate pancreatic enzyme activation. METHODS: To study this hypothesis in vitro, explants of the bovine main pancreatic duct were isolated and maintained in primary culture. They were then mounted in Ussing chambers, and bicarbonate secretion was determined with an autoburette titration. The response to luminal or serosal trypsin (10 micromol/L) and the synthetic trypsin receptor activating peptide (TRAP) (30 micromol/L) on spontaneous and secretin-stimulated bicarbonate secretion (10 nmol/L) was examined. RESULTS: Serosal trypsin had no effect. Both luminal trypsin and TRAP significantly reduced the spontaneous bicarbonate secretion observed at luminal pH 7.4 (2.8 +/- 0.2 - 0.4 +/- 0.1 micromol/hr/cm(2) and 4.0 +/- 1.2 - 1.6 +/- 0.4 micromol/hr/cm(2), respectively) in a reversible manner. Baseline bicarbonate secretion at luminal pH 8.0 was reduced by trypsin and TRAP, but the increase in response to secretin stimulation observed with controls was unaffected. CONCLUSIONS: PAR-2 activation may be the mechanism by which pancreatic juice secretion is inhibited during pancreatitis. We suggest that pharmacologic activation of PAR-2 receptors could suppress pancreatic exocrine secretion and thus serve as a potential agent in the treatment and prevention of pancreatic fistulas.
Carlos Alvarez; Joseph P Regan; Demetri Merianos; Barbara L Bass
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Surgery     Volume:  136     ISSN:  0039-6060     ISO Abbreviation:  Surgery     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-06     Completed Date:  2004-10-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417347     Medline TA:  Surgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  669-76     Citation Subset:  AIM; IM    
Department of Surgery, University of Medicine and Dentistry of New Jersey - New Jersey Medical School, Newark, NJ, USA.
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MeSH Terms
Bicarbonates / metabolism*
Cells, Cultured
Pancreatic Ducts / cytology,  drug effects,  metabolism*
Receptor, PAR-2 / agonists,  metabolism*
Serine Endopeptidases / pharmacology
Trypsin / pharmacology
Reg. No./Substance:
0/Bicarbonates; 0/Receptor, PAR-2; EC 3.4.21.-/Serine Endopeptidases; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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