Reactome | ANO1 inhibitors bind ANO1

ANO1 inhibitors bind ANO1

Stable Identifier

R-HSA-9659611

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

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Calcium-activated chloride channels (CaCCs) are ubiquitously expressed and implicated in physiological processes such as sensory transduction, fertilization, epithelial secretion, and smooth muscle contraction. Anoctamin 1 (ANO1, TMEM16A) is a Ca(2+)-activated Cl(-) channel (CACC) expressed in smooth muscle and epithelial cells and highly expressed in interstitial cells of Cajal throughout the GI tract (Sanders et al. 2012). ANO1, amongst other ion channels, generates electrical activity that drives contractility in the GI tract (Yang et al. 2008, Scudieri et al. 2012). Crofelemer is a purified proanthocyanidin oligomer extracted from the bark latex of Croton lechleri used for the treatment of diarrhoea associated with anti-HIV drugs (Yeo et al. 2013). Crofelemer was found to strongly inhibit the intestinal ANO1 by a voltage-independent inhibition mechanism (Tradtrantip et al. 2010). ANO1 blockers like niflumic acid have been shown to block slow waves, which produce motility, in the human intestine (Sanders et al. 2012). Anthracene-9-carboxylic acid (A9C) is an open ANO1 channel blocker and gating modifier (Ta et al. 2016).

Literature References

PubMed ID	Title	Journal	Year
19808995	Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels Tradtrantip, L, Namkung, W, Verkman, AS	Mol. Pharmacol.	2010
18724360	TMEM16A confers receptor-activated calcium-dependent chloride conductance Yang, YD, Cho, H, Koo, JY, Tak, MH, Cho, Y, Shim, WS, Park, SP, Lee, J, Lee, B, Kim, BM, Raouf, R, Shin, YK, Oh, U	Nature	2008
22002868	Anoctamins and gastrointestinal smooth muscle excitability Sanders, KM, Zhu, MH, Britton, F, Koh, SD, Ward, SM	Exp. Physiol.	2012
26359375	A novel exon in the human Ca2+-activated Cl- channel Ano1 imparts greater sensitivity to intracellular Ca2 Strege, PR, Bernard, CE, Mazzone, A, Linden, DR, Beyder, A, Gibbons, SJ, Farrugia, G	Am. J. Physiol. Gastrointest. Liver Physiol.	2015
21984732	The anoctamin family: TMEM16A and TMEM16B as calcium-activated chloride channels Scudieri, P, Sondo, E, Ferrera, L, Galietta, LJ	Exp. Physiol.	2012
26562072	Mechanism of allosteric activation of TMEM16A/ANO1 channels by a commonly used chloride channel blocker Ta, CM, Adomaviciene, A, Rorsman, NJ, Garnett, H, Tammaro, P	Br. J. Pharmacol.	2016
23616951	Crofelemer, a novel antisecretory agent approved for the treatment of HIV-associated diarrhea Yeo, QM, Crutchley, R, Cottreau, J, Tucker, A, Garey, KW	Drugs Today	2013