Protease-activated receptor 2 in the enteric nervous system

Danielle M. Fritze, Michael W. Mulholland, Weizhen Zhang

Research output: Chapter in Book/Report/Conference proceedingChapter


The enteric nervous system (ENS) integrates local neuroendocrine signaling with central autonomic input to regulate the motor and secretory function of the gastrointestinal (GI) tract. Exposure to inflammatory mediators such as trypsin or mast cell tryptase is postulated to affect ENS signaling, contributing to both protective and pathologic changes in GI function. Protease-activated receptor 2 (PAR-2) is a receptor specifically activated by the serine-proteases trypsin and tryptase. Within the mammalian ENS, PAR-2 expression has been identified in neurons of both the submucosal and myenteric plexus. Myenteric neurons respond to trypsin with prolonged depolarization, suppression of fast excitatory post-synaptic potentials, and phospholipase C (PLC) - dependent cytosolic calcium transients. Trypsin also activates PAR-2 in enteroglial cells, causing activation of PLC and sphingosine kinase. This signaling cascade results in cytosolic calcium transients, subsequent capacitative calcium entry, and c-fos expression. Activation of PAR-2 by trypsin within the ENS may ultimately alter intestinal ion channel permeability and secretory function. PAR-2 may therefore contribute to the physiological function and pathophysiological response in the ENS.

Original languageEnglish (US)
Title of host publicationTrypsin
Subtitle of host publicationStructure, Biosynthesis and Functions
PublisherNova Science Publishers, Inc.
Number of pages16
ISBN (Print)9781619423190
StatePublished - Dec 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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