Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system
| Autor: | Peter Holzer |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
TNBS
trinitrobenzene sulfonic acid CCK cholecystokinin TRPC6 TRPP TRPM transient receptor potential melastatin Inflammatory bowel disease TRPC4 CGRP calcitonin gene-related peptide Transient receptor potential channel Transient Receptor Potential Channels TRPA transient receptor potential ankyrin siRNA small interfering ribonucleic acid Pharmacology (medical) ICC interstitial cell of Cajal 5-HT 5-hydroxytryptamine Chemistry Smooth muscle contraction GI gastrointestinal DRG dorsal root ganglion AITC allyl isothiocyanate Hyperalgesia Taste TRP transient receptor potential TRPV4 medicine.medical_specialty Digestive System Diseases mRNA messenger ribonucleic acid Chemesthesis TRPM5 Transducers TRPM6 Pain PKD polycystic kidney disease TRPA1 Article Gastrointestinal cancer TRPM7 DSS dextran sulfate sodium Internal medicine Chemosensation Hypersensitivity medicine Animals Humans TRPP transient receptor potential polycystin TRPV transient receptor potential vanilloid GPCR G protein-coupled receptor Inflammation Pharmacology Gastrointestinal motility Mechanosensation TRPV1 Endocrinology RNA ribonucleic acid PAR protease-activated receptor TRPC transient receptor potential canonical (or classical) TRPV6 |
| Zdroj: | Pharmacology & Therapeutics |
| ISSN: | 0163-7258 |
| DOI: | 10.1016/j.pharmthera.2011.03.006 |
| Popis: | Approximately 20 of the 30 mammalian transient receptor potential (TRP) channel subunits are expressed by specific neurons and cells within the alimentary canal. They subserve important roles in taste, chemesthesis, mechanosensation, pain and hyperalgesia and contribute to the regulation of gastrointestinal motility, absorptive and secretory processes, blood flow, and mucosal homeostasis. In a cellular perspective, TRP channels operate either as primary detectors of chemical and physical stimuli, as secondary transducers of ionotropic or metabotropic receptors, or as ion transport channels. The polymodal sensory function of TRPA1, TRPM5, TRPM8, TRPP2, TRPV1, TRPV3 and TRPV4 enables the digestive system to survey its physical and chemical environment, which is relevant to all processes of digestion. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 contribute to the absorption of Ca2+ and Mg2+, respectively. TRPM7 participates in intestinal pacemaker activity, and TRPC4 transduces muscarinic acetylcholine receptor activation to smooth muscle contraction. Changes in TRP channel expression or function are associated with a variety of diseases/disorders of the digestive system, notably gastro-esophageal reflux disease, inflammatory bowel disease, pain and hyperalgesia in heartburn, functional dyspepsia and irritable bowel syndrome, cholera, hypomagnesemia with secondary hypocalcemia, infantile hypertrophic pyloric stenosis, esophageal, gastrointestinal and pancreatic cancer, and polycystic liver disease. These implications identify TRP channels as promising drug targets for the management of a number of gastrointestinal pathologies. As a result, major efforts are put into the development of selective TRP channel agonists and antagonists and the assessment of their therapeutic potential. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect