Protease-activated receptors: potential therapeutic targets in irritable bowel syndrome?
Protease-activated receptors (PARs) are a family of four G-protein-coupled receptors (PAR-1 to PAR-4) activated by the proteolytic cleavage of their N-terminal extracellular domain. This activation first involves the recognition of the extracellular domain by proteases, such as thrombin, but also trypsin or tryptase which are particularly abundant in the gastrointestinal tract, both under physiological circumstances and in several digestive diseases. Activation of PARs, particularly of PAR-1 and -2, modulates intestinal functions, such as gastrointestinal motility, visceral nociception, mucosal inflammatory response, and epithelial functions (intestinal secretion and permeability). As these physiological properties have been shown to be altered in various extents and combinations in different clinical presentations of irritable bowel syndrome, PARs appear as putative targets for future therapeutic intervention in these patients.
Gloro
Romain
R
Centre Hospitalier Universitaire de Caen, Service d'Hépato-Gastro-Entérologie et Nutrition, Avenue de la Côte de Nacre, 14033 Caen Cedex, France.
Ducrotte
Philippe
P
Reimund
Jean-Marie
JM
D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000378:metabolism*; D044462:Receptors, Proteinase-Activated / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D044462:Receptors, Proteinase-Activated