Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Jul;131(1):142-70.
doi: 10.1016/j.pharmthera.2011.03.006. Epub 2011 Mar 21.

Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

Peter Holzer  1
Affiliations
Review

Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

Peter Holzer. Pharmacol Ther. 2011 Jul.

Abstract

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Diagram portraying 3 different molecular roles of TRP channels in the digestive system: (1) TRP channels as molecular sensors (detectors or primary transducers) of chemical and physical stimuli, (2) TRP channels as secondary transducers (downstream transducers or effectors) of cell activation induced by G protein-coupled receptors or ion channel receptors, and (3) TRP channels as Ca2+ or Mg2+ transport channels.
Fig. 2
Fig. 2
Overview of the functional implications of TRP channels in the digestive system.
Fig. 3
Fig. 3
Overview of the associations of TRP channels with diseases and disorders of the digestive system.
Fig. 4
Fig. 4
Overview of the therapeutic potential of TRP channel ligands in diseases and disorders of the digestive system.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ahern G.P., Wang X., Miyares R.L. Polyamines are potent ligands for the capsaicin receptor TRPV1. J Biol Chem. 2006;281:8991–8995. - PubMed
    1. Aihara E., Hayashi M., Sasaki Y., Kobata A., Takeuchi K. Mechanisms underlying capsaicin-stimulated secretion in the stomach: comparison with mucosal acidification. J Pharmacol Exp Ther. 2005;315:423–432. - PubMed
    1. Ajibade D.V., Dhawan P., Fechner A.J., Meyer M.B., Pike J.W., Christakos S. Evidence for a role of prolactin in calcium homeostasis: regulation of intestinal transient receptor potential vanilloid type 6, intestinal calcium absorption, and the 25-hydroxyvitamin D3 1alpha hydroxylase gene by prolactin. Endocrinology. 2010;151:2974–2984. - PMC - PubMed
    1. Akbar A., Yiangou Y., Facer P., Brydon W.G., Walters J.R., Anand P. Expression of the TRPV1 receptor differs in quiescent inflammatory bowel disease with or without abdominal pain. Gut. 2010;59:767–774. - PubMed
    1. Akbar A., Yiangou Y., Facer P., Walters J.R., Anand P., Ghosh S. Increased capsaicin receptor TRPV1 expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain. Gut. 2008;57:923–929. - PMC - PubMed

Publication types

MeSH terms

Substances