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Proteinase-activated receptors.

S R Macfarlane1, M J Seatter, T Kanke

  • 1Department of Physiology and Pharmacology, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, Glasgow, United Kingdom.

Pharmacological Reviews
|May 18, 2001
PubMed
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Proteinase-activated receptors (PARs) are G-protein-coupled receptors activated by protease cleavage. Research explores PAR-1 roles in vascular disorders and cancer, and PAR-2 activation by various proteases in physiological and pathological contexts.

Area of Science:

  • Biochemistry
  • Cellular Biology
  • Pharmacology

Background:

  • Proteinase-activated receptors (PARs) are a novel family of seven-transmembrane G-protein-coupled receptors.
  • Unlike typical receptors, PARs activate upon cleavage of their N-terminus by serine proteases, generating a tethered ligand.

Purpose of the Study:

  • To review the distinct N-terminal cleavage sites and pharmacology of identified PARs (PAR-1, PAR-2, PAR-3, PAR-4).
  • To discuss the role of thrombin and PAR-1 antagonists in wound healing, vascular disorders, and cancer.
  • To assess PAR-2 activation mechanisms, signaling, desensitization, and its roles in various tissues.

Main Methods:

  • Literature review and synthesis of existing research on PARs.
  • Analysis of PAR-1 and PAR-2 signaling pathways and desensitization processes.

Related Experiment Videos

  • Consideration of physiological and pathophysiological roles based on protease activation.

    • Main Results:

    • Four PARs have been identified, each with unique activation properties.
    • PAR-1 is implicated in vascular disorders and cancer, with ongoing development of antagonists.
    • PAR-2 can be activated by multiple serine proteases, suggesting broad physiological and pathophysiological relevance in tissues like skin and intestine.

    Conclusions:

    • PARs represent a complex system with diverse roles in health and disease.
    • Further research is needed to fully elucidate the functions of all PARs and their interactions, especially concerning thrombin's multifaceted effects.
    • The discovery of new PARs and activation mechanisms is a key future direction.