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Research Article Free access | 10.1172/JCI119658

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

C U Corvera, O Déry, K McConalogue, S K Böhm, L M Khitin, G H Caughey, D G Payan, and N W Bunnett

Department of Surgery, University of California, San Francisco, San Francisco, California 94143-0660, USA.

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Department of Surgery, University of California, San Francisco, San Francisco, California 94143-0660, USA.

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Department of Surgery, University of California, San Francisco, San Francisco, California 94143-0660, USA.

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Department of Surgery, University of California, San Francisco, San Francisco, California 94143-0660, USA.

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Department of Surgery, University of California, San Francisco, San Francisco, California 94143-0660, USA.

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Department of Surgery, University of California, San Francisco, San Francisco, California 94143-0660, USA.

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Department of Surgery, University of California, San Francisco, San Francisco, California 94143-0660, USA.

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Department of Surgery, University of California, San Francisco, San Francisco, California 94143-0660, USA.

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First published September 15, 1997 - More info

Published in Volume 100, Issue 6 (September 15, 1997)
J Clin Invest. 1997;100(6):1383–1393. doi:10.1172/JCI119658.
Copyright © 1997, The American Society for Clinical Investigation.
Published September 15, 1997
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-NG-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.

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