Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Pharm Biol
2021 Dec 01;591:1008-1015. doi: 10.1080/13880209.2021.1949357.
Show Gene links
Show Anatomy links
Cucumis sativus extract elicits chloride secretion by stimulation of the intestinal TMEM16A ion channel.
Saha T
,
Aoun J
,
Sarkar P
,
Bourdelais AJ
,
Baden DG
,
Leblanc N
,
Hamlyn JM
,
Woodward OM
,
Hoque KM
.
???displayArticle.abstract???
CONTEXT: Cucumber (Cucumis sativus Linn. [Cucurbitaceae]) is widely known for its purgative, antidiabetic, antioxidant, and anticancer therapeutic potential. However, its effect on gastrointestinal (GI) disease is unrecognised.
OBJECTIVE: This study investigated the effect of C. sativus fruit extract (CCE) on intestinal chloride secretion, motility, and motor function, and the role of TMEM16A chloride channels.
MATERIALS AND METHODS: CCE extracts were obtained from commercially available cucumber. Active fractions were then purified by HPLC and analysed by high resolution mass spectrometry. The effect of CCE on intestinal chloride secretion was investigated in human colonic T84 cells, ex vivo mouse intestinal tissue using an Ussing chamber, and the two-electrode voltage-clamp technique to record calcium sensitive TMEM16A chloride currents in Xenopus laevis oocytes. In vivo, intestinal motility was investigated using the loperamide-induced C57BL/6 constipation mouse model. Ex vivo contractility of mouse colonic smooth muscles was assessed by isometric force measurements.
RESULTS: CCE increased the short-circuit current (ΔIsc 34.47 ± µA/cm2) and apical membrane chloride conductance (ΔICl 95 ± 8.1 µA/cm2) in intestinal epithelial cells. The effect was dose-dependent, with an EC50 value of 0.06 µg/mL. CCE stimulated the endogenous TMEM16A-induced Cl- current in Xenopus laevis oocytes. Moreover, CCE increased the contractility of smooth muscle in mouse colonic tissue and enhanced small bowel transit in CCE treated mice compared to loperamide controls. Mass spectrometry suggested a cucurbitacin-like analogue with a mass of 512.07 g/mol underlying the bioactivity of CCE.
CONCLUSION: A cucurbitacin-like analog present in CCE activates TMEM16A channels, which may have therapeutic potential in cystic fibrosis and intestinal hypodynamic disorders.
Aoun,
Anoctamin 6 Contributes to Cl- Secretion in Accessory Cholera Enterotoxin (Ace)-stimulated Diarrhea: AN ESSENTIAL ROLE FOR PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE (PIP2) SIGNALING IN CHOLERA.
2016, Pubmed
Aoun,
Anoctamin 6 Contributes to Cl- Secretion in Accessory Cholera Enterotoxin (Ace)-stimulated Diarrhea: AN ESSENTIAL ROLE FOR PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE (PIP2) SIGNALING IN CHOLERA.
2016,
Pubmed
Begenisich,
Regulation of chloride channels in secretory epithelia.
1998,
Pubmed
Callamaras,
Ca(2+)-dependent activation of Cl(-) currents in Xenopus oocytes is modulated by voltage.
2000,
Pubmed
,
Xenbase
Caputo,
TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity.
2008,
Pubmed
Chen,
Differential gene expression in functional classes of interstitial cells of Cajal in murine small intestine.
2007,
Pubmed
Flores,
TMEM16 proteins: the long awaited calcium-activated chloride channels?
2009,
Pubmed
,
Xenbase
Forrest,
Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary hypertension.
2012,
Pubmed
Frizzell,
Electrophysiology of chloride-secreting epithelia.
1981,
Pubmed
Gomez-Pinilla,
Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract.
2009,
Pubmed
Hoque,
Epac1 mediates protein kinase A-independent mechanism of forskolin-activated intestinal chloride secretion.
2010,
Pubmed
Hwang,
Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles.
2009,
Pubmed
Kim,
Cucurbitacin B Induces Hypoglycemic Effect in Diabetic Mice by Regulation of AMP-Activated Protein Kinase Alpha and Glucagon-Like Peptide-1 via Bitter Taste Receptor Signaling.
2018,
Pubmed
Kojima,
Characterization of two models of drug-induced constipation in mice and evaluation of mustard oil in these models.
2009,
Pubmed
Mukherjee,
Phytochemical and therapeutic potential of cucumber.
2013,
Pubmed
Olivier,
Animal models of gastrointestinal and liver diseases. Animal models of cystic fibrosis: gastrointestinal, pancreatic, and hepatobiliary disease and pathophysiology.
2015,
Pubmed
Ousingsawat,
Loss of TMEM16A causes a defect in epithelial Ca2+-dependent chloride transport.
2009,
Pubmed
Sabharwal,
Gastrointestinal Manifestations of Cystic Fibrosis.
2016,
Pubmed
Schroeder,
Expression cloning of TMEM16A as a calcium-activated chloride channel subunit.
2008,
Pubmed
,
Xenbase
Sheikh,
The Epac1 signaling pathway regulates Cl- secretion via modulation of apical KCNN4c channels in diarrhea.
2013,
Pubmed
Woodward,
Identification of a polycystin-1 cleavage product, P100, that regulates store operated Ca entry through interactions with STIM1.
2010,
Pubmed
,
Xenbase
Yang,
TMEM16A confers receptor-activated calcium-dependent chloride conductance.
2008,
Pubmed
,
Xenbase
Zhu,
A Ca(2+)-activated Cl(-) conductance in interstitial cells of Cajal linked to slow wave currents and pacemaker activity.
2009,
Pubmed
Zhu,
Inhibitory activities of curzerenone, curdione, furanodienone, curcumol and germacrone on Ca2+-activated chloride channels.
2020,
Pubmed