ARTICLE

Characterization of Protease-activated Receptor-2 Immunoreactivity in Normal Human Tissues

Correspondence to: Patricia Andrade-Gordon, R.W. Johnson Pharmaceutical Research Institute, Welsh and McKean Roads, Spring House, PA 19477.

PAR-2 is a second member of a novel family of G-protein-coupled receptors characterized by a proteolytic cleavage of the amino terminus, thus exposing a tethered peptide ligand that autoactivates the receptor. The physiological and/or pathological role(s) of PAR-2 are still unknown. This study provides tissue-specific cellular localization of PAR-2 in normal human tissues by immunohistochemical techniques. A polyclonal antibody, PAR-2C, was raised against a peptide corresponding to the amino terminal sequence SLIGKVDGTSHVTGKGV of human PAR-2. Significant PAR-2 immunoreactivity was detected in smooth muscle of vascular and nonvascular origin and stromal cells from a variety of tissues. PAR-2 was also present in endothelial and epithelial cells independent of tissue type. Strong immunolabeling was observed throughout the gastrointestinal tract, indicating a possible function for PAR-2 in this system. In the CNS, PAR-2 was localized to many astrocytes and neurons, suggesting involvement of PAR-2 in neuronal function. A role for PAR-2 in the skin was further supported by its immunolocalization in the epidermis. PAR-2C antibody exemplifies an important tool to address the physiological role(s) of PAR-2. (J Histochem Cytochem 46:157—164, 1998)

Key Words: PAR-2 (protease activated, receptor 2), PAR-1 (thrombin receptor), human, immunohistochemistry, flow cytometry

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				D Miotto, M D Hollenberg, N W Bunnett, A Papi, F Braccioni, P Boschetto, F Rea, A Zuin, P Geppetti, M Saetta, et al. Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers Thorax, February 1, 2002; 57(2): 146 - 151. [Abstract] [Full Text] [PDF]

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				P. Berger, D.-W. Perng, H. Thabrew, S. J. Compton, J. A Cairns, A. R. McEuen, R. Marthan, J.-M. Tunon De Lara, and A. F. Walls Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells J Appl Physiol, September 1, 2001; 91(3): 1372 - 1379. [Abstract] [Full Text] [PDF]

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				S. R. Macfarlane, M. J. Seatter, T. Kanke, G. D. Hunter, and R. Plevin Proteinase-Activated Receptors Pharmacol. Rev., June 1, 2001; 53(2): 245 - 282. [Abstract] [Full Text] [PDF]

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