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Journal of Histochemistry and Cytochemistry, Vol. 46, 157-164, Copyright © 1998 by The Histochemical Society, Inc.

ARTICLE

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

Michael R. D'Andreaa, Claudia K. Deriana, Didier Leturcqb, Sherry M. Bakerb, Anders Brunmarkb, Ping Lingb, Andrew L. Darrowa, Rosemary J. Santullia, Lawrence F. Brassc, and Patricia Andrade-Gordona
a Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania
b Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, La Jolla, California
c Department of Medicine and Pathology, University of Pennsylvania, Philadelphia, Pennsylvania

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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C. G. Sobey, J. D. Moffatt, T. M. Cocks, and H. A. Kontos
Evidence for Selective Effects of Chronic Hypertension on Cerebral Artery Vasodilatation to Protease-Activated Receptor-2 Activation • Editorial Comment
Stroke, September 1, 1999; 30(9): 1933 - 1941.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
C. Cicala, A. Pinto, M. Bucci, R. Sorrentino, B. Walker, P. Harriot, A. Cruchley, S. Kapas, G. L. Howells, and G. Cirino
Protease-Activated Receptor-2 Involvement in Hypotension in Normal and Endotoxemic Rats In Vivo
Circulation, May 18, 1999; 99(19): 2590 - 2597.
[Abstract] [Full Text] [PDF]

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 J Biomol ScreenHome page
B. R. Conway, L. K. Minor, J. Z. Xu, J. W. Gunnet, R. DeBiasio, M. R. D'Andrea, R. Rubin, R. DeBiasio, K. Giuliano, L. Zhou, et al.
Quantification of G-Protein Coupled Receptor Internalization Using G-Protein Coupled Receptor-Green Fluorescent Protein Conjugates with the ArrayScanTM High-Content Screening System
J Biomol Screen, April 1, 1999; 4(2): 75 - 86.
[Abstract] [PDF]

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 J. Pharmacol. Exp. Ther.Home page
B. P. Damiano, W.-M. Cheung, R. J. Santulli, W.-P. Fung-Leung, K. Ngo, R. D. Ye, A. L. Darrow, C. K. Derian, L. de Garavilla, and P. Andrade-Gordon
Cardiovascular Responses Mediated by Protease-Activated Receptor-2 (PAR-2) and Thrombin Receptor (PAR-1) are Distinguished in Mice Deficient in PAR-2 or PAR-1
J. Pharmacol. Exp. Ther., February 1, 1999; 288(2): 671 - 678.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
T. Kanke, S. R. Macfarlane, M. J. Seatter, E. Davenport, A. Paul, R. C. McKenzie, and R. Plevin
Proteinase-activated Receptor-2-mediated Activation of Stress-activated Protein Kinases and Inhibitory kappa B Kinases in NCTC 2544 Keratinocytes
J. Biol. Chem., August 17, 2001; 276(34): 31657 - 31666.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. J. Ubl, Z. V. Grishina, T. K. Sukhomlin, T. Welte, F. Sedehizade, and G. Reiser
Human bronchial epithelial cells express PAR-2 with different sensitivity to thermolysin
Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1339 - L1348.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
C. Napoli, F. De Nigris, C. Cicala, J. L. Wallace, G. Caliendo, M. Condorelli, V. Santagada, and G. Cirino
Protease-activated receptor-2 activation improves efficiency of experimental ischemic preconditioning
Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2004 - H2010.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
P. G. McLean, D. Aston, D. Sarkar, and A. Ahluwalia
Protease-Activated Receptor-2 Activation Causes EDHF-Like Coronary Vasodilation: Selective Preservation in Ischemia/Reperfusion Injury: Involvement of Lipoxygenase Products, VR1 Receptors, and C-Fibers
Circ. Res., March 8, 2002; 90(4): 465 - 472.
[Abstract] [Full Text] [PDF]



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