Proteinase-activated receptor pharmacology: trickier and trickier

Proteinase-activated receptors (PARs) are G-protein-coupled receptors for serine and other proteinases. Peptide agonists of these receptors are frequently used to characterise the presence and role of PARs in cells and organ systems. However, the specificity of these peptides is questionable in some assay systems. In this issue, Hollenberg et al. report very different effects of PAR(4) receptors in various assays. Their results suggest the existence of unknown receptors and further highlight the need to use peptide PAR agonists with due caution.