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.
|Title of host publication
|Subtitle of host publication
|Structure, Biosynthesis and Functions
|Nova Science Publishers, Inc.
|Number of pages
|Published - Dec 1 2012
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology