Protease-activated receptor-2 regulates bicarbonate secretion by pancreatic duct cells in vitro

Carlos Alvarez, Joseph P. Regan, Demetri Merianos, Barbara L. Bass

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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 μmol/L) and the synthetic trypsin receptor activating peptide (TRAP) (30 μmol/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 μmol/hr/cm2 and 4.0 ± 1.2 - 1.6 ± 0.4 μmol/hr/cm2, 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.

Original languageEnglish (US)
Pages (from-to)669-676
Number of pages8
JournalSurgery
Volume136
Issue number3
DOIs
StatePublished - Sep 1 2004

ASJC Scopus subject areas

  • Surgery

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