Protease-activated receptor-2 regulates bicarbonate secretion by pancreatic duct cells in vitro.
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.
Alvarez
Carlos
C
Department of Surgery, University of Medicine and Dentistry of New Jersey - New Jersey Medical School, Newark, NJ, USA.
Regan
Joseph P
JP
Merianos
Demetri
D
Bass
Barbara L
BL
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000819:agonists / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
D001639:Bicarbonates; D044464:Receptor, PAR-2; D012697:Serine Endopeptidases; D014357:Trypsin