Interest in the development of specific antagonists of the protease-activated receptors are significant, however, achieving such goals remain extremely challenging. Considerable efforts have been directed at developing specific antagonists of the first elucidated member of this receptor family, namely the thrombin receptor, PAR-1. However, significantly less effort has been directed at the second member of the family, PAR-2 due in part to lack of clarity concerning its activating protease(s), and uncertainty concerning its physiological and pathophysiological roles in disease pathways. This review will briefly summarize what is known about the activating protease(s), the potential (patho)physiological roles for PAR-2 and structure-activity relationships that have been developed for PAR-2 agonists and antagonists in relationship to agonists and antagonists developed for the other protease-activated receptors.
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