Protease-activated receptor-2 protects against pancreatitis by stimulating exocrine secretion

Vijay P. Singh, Lakshmi Bhagat, Sarah Navina, Rifat Sharif, Rajinder Dawra, Ashok Saluja

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background: Protease-activated receptor-2 (PAR-2) is present in the pancreas, where it has been shown to play a protective role during pancreatitis. However, the mechanism by which it protects against pancreatitis still remains to be elucidated. Acute pancreatitis is associated with premature zymogen activation and a blockage in digestive enzyme secretion. Aim: To examine the effects of PAR-2 activation on the severity of pancreatitis, and to determine whether its protective effects are mediated by affecting either premature activation or secretory blockage, or both. Results: The results confirmed that PAR-2 -/- mice have more severe pancreatitis than wild-type mice. Interestingly, intrapancreatic trypsin levels in the PAR-2 knockouts remained high after 6 h of pancreatitis, whereas they reverted to normal in the wild types. During pancreatitis, PAR-2 mRNA levels were upregulated in wild-type mice in response to supramaximal caerulein administration. Further, after a single injection of supramaximal caerulein, PAR-2 mRNA levels were also elevated, reaching a peak at 3 h. Stimulating PAR-2 with trypsin or the PAR-2-activating peptide, serine-leucine-isoleucine-glycine-arginine-leucine (SLIGRL), induced significantly more secretion from the acini of these caerulein-sensitised mice compared with the controls. PAR-2 activation also reversed the inhibition of secretion observed in both the caerulein and arginine models. Conclusions: Trypsin released during the early stages of pancreatitis activates PAR-2 receptors on the acinar cells and stimulates secretion from these cells. Thus, PAR-2 activation may decrease pancreatic injury and limit the severity of pancreatitis by allowing extracellular trypsin to act as a secretogogue.

Original languageEnglish (US)
Pages (from-to)958-964
Number of pages7
JournalGut
Volume56
Issue number7
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

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PAR-2 Receptor
Pancreatitis
Ceruletide
Trypsin
Leucine
Arginine
Messenger RNA
Enzyme Precursors
Isoleucine
Acinar Cells
Glycine
Serine
Pancreas

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Protease-activated receptor-2 protects against pancreatitis by stimulating exocrine secretion. / Singh, Vijay P.; Bhagat, Lakshmi; Navina, Sarah; Sharif, Rifat; Dawra, Rajinder; Saluja, Ashok.

In: Gut, Vol. 56, No. 7, 01.07.2007, p. 958-964.

Research output: Contribution to journalArticle

Singh, Vijay P. ; Bhagat, Lakshmi ; Navina, Sarah ; Sharif, Rifat ; Dawra, Rajinder ; Saluja, Ashok. / Protease-activated receptor-2 protects against pancreatitis by stimulating exocrine secretion. In: Gut. 2007 ; Vol. 56, No. 7. pp. 958-964.
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