Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Protease-activated receptors: potential therapeutic targets in irritable bowel syndrome? 1618 59

Protease-activated receptors (PARs) are a unique class of G-protein-coupled transmembrane receptors, which revolutionized the perception of proteases from degradative enzymes to context-specific signaling factors. Although PARs are traditionally known to affect several vascular responses, recent investigations have started to pinpoint the functional role of PAR signaling in the gastrointestinal (GI) tract. This organ is exposed to the highest number of proteases, either from the gut lumen or from the mucosa. Luminal proteases include the host's digestive enzymes and the proteases released by the commensal microbiota, while mucosal proteases entail extravascular clotting factors and the enzymes released from resident and infiltrating immune cells. Active proteases and, in case of a disrupted gut barrier, even entire microorganisms are capable to translocate the intestinal epithelium, particularly under inflammatory conditions. Especially PAR-1 and PAR-2, expressed throughout the GI tract, impact gut permeability regulation, a major factor affecting intestinal physiology and metabolic inflammation. In addition, PARs are critically involved in the onset of inflammatory bowel diseases, irritable bowel syndrome, and tumor progression. Due to the number of proteases involved and the multiple cell types affected, selective regulation of intestinal PARs represents an interesting therapeutic strategy. The analysis of tissue/cell-specific knockout animal models will be of crucial importance to unravel the intrinsic complexity of this signaling network. Here, we provide an overview on the implication of PARs in intestinal permeability regulation under physiologic and disease conditions.
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PMID:Protease-activated receptor signaling in intestinal permeability regulation. 3149 63