Mast cell tryptase regulates rat colonic myocytes through proteinase- activated receptor 2

Carlos U. Corvera, Olivier Déry, K. McConalogue, Stephan K. Böhm, Lev M. Khitin, George H. Caughey, Donald G. Payan, Nigel W. Bunnett

Research output: Contribution to journalArticle

Abstract

Proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin-like enzymes. PAR-2 is highly expressed by small intestinal enterocytes where it is activated by luminal trypsin. The location, mechanism of activation, and biological functions of PAR-2 in the colon, however, are unknown. We localized PAR-2 to the muscularis externa of the rat colon by immunofluorescence. Myocytes in primary culture also expressed PAR-2, assessed by immunofluorescence and RT- PCR. Trypsin, SLIGRL-NH2 (corresponding to the PAR-2 tethered ligand), mast cell tryptase, and a filtrate of degranulated mast cells stimulated a prompt increase in [Ca2+](i) in myocytes. The response to tryptase and the mast cell filtrate was inhibited by the tryptase inhibitor BABIM, and abolished by desensitization of PAR-2 with trypsin. PAR-2 activation inhibited the amplitude of rhythmic contractions of strips of rat colon. This response was unaffected by indomethacin, L-N(G)-nitroarginine methyl ester, a bradykinin B2 receptor antagonist and tetrodotoxin. Thus, PAR-2 is highly expressed by colonic myocytes where it may be cleaved and activated by mast cell tryptase. This may contribute to motility disturbances of the colon during conditions associated with mast cell degranulation.

Original languageEnglish (US)
Pages (from-to)1383-1393
Number of pages11
JournalJournal of Clinical Investigation
Volume100
Issue number6
DOIs
StatePublished - Sep 15 1997

Keywords

  • Ileus
  • Inflammation
  • Smooth muscle
  • Trypsin

ASJC Scopus subject areas

  • Medicine(all)

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    Corvera, C. U., Déry, O., McConalogue, K., Böhm, S. K., Khitin, L. M., Caughey, G. H., Payan, D. G., & Bunnett, N. W. (1997). Mast cell tryptase regulates rat colonic myocytes through proteinase- activated receptor 2. Journal of Clinical Investigation, 100(6), 1383-1393. https://doi.org/10.1172/JCI119658