TRP channels in neurogastroenterology: opportunities for therapeutic intervention

被引:75
作者
Boesmans, Werend [1 ]
Owsianik, Grzegorz [2 ]
Tack, Jan [1 ]
Voets, Thomas [2 ]
Vanden Berghe, Pieter [1 ]
机构
[1] Katholieke Univ Leuven, TARGID Translat Res Ctr Gastrointestinal Disorder, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven, Lab Ion Channel Res, B-3000 Louvain, Belgium
关键词
enteric nervous system; visceral afferents; gastrointestinal motility; sensory transmission; hypersensitivity; transient receptor potential cation channels; RECEPTOR POTENTIAL CHANNELS; COLONIC SPLANCHNIC AFFERENTS; MAST-CELL ACTIVATION; GENE-RELATED PEPTIDE; CAPSAICIN-RECEPTOR; INTERSTITIAL-CELLS; CATION CHANNEL; VANILLOID RECEPTOR; VISCERAL PAIN; ION-CHANNEL;
D O I
10.1111/j.1476-5381.2010.01009.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The members of the superfamily of transient receptor potential (TRP) cation channels are involved in a plethora of cellular functions. During the last decade, a vast amount of evidence is accumulating that attributes an important role to these cation channels in different regulatory aspects of the alimentary tract. In this review we discuss the expression patterns and roles of TRP channels in the regulation of gastrointestinal motility, enteric nervous system signalling and visceral sensation, and provide our perspectives on pharmacological targeting of TRPs as a strategy to treat various gastrointestinal disorders. We found that the current knowledge about the role of some members of the TRP superfamily in neurogastroenterology is rather limited, whereas the function of other TRP channels, especially of those implicated in smooth muscle cell contractility (TRPC4, TRPC6), visceral sensitivity and hypersensitivity (TRPV1, TRPV4, TRPA1), tends to be well established. Compared with expression data, mechanistic information about TRP channels in intestinal pacemaking (TRPC4, TRPC6, TRPM7), enteric nervous system signalling (TRPCs) and enteroendocrine cells (TRPM5) is lacking. It is clear that several different TRP channels play important roles in the cellular apparatus that controls gastrointestinal function. They are involved in the regulation of gastrointestinal motility and absorption, visceral sensation and visceral hypersensitivity. TRP channels can be considered as interesting targets to tackle digestive diseases, motility disorders and visceral pain. At present, TRPV1 antagonists are under development for the treatment of heartburn and visceral hypersensitivity, but interference with other TRP channels is also tempting. However, their role in gastrointestinal pathophysiology first needs to be further elucidated.
引用
收藏
页码:18 / 37
页数:20
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