CFTR chloride channel as a molecular target of anthraquinone compounds in herbal laxatives

Abstract

Aim: To clarify whether CFTR is a molecular target of intestinal fluid secretion caused by the anthraquinone compounds from laxative herbal plants. Methods: A cell-based fluorescent assay to measure I -influx through CFTR chloride channel. A short-circuit current assay to measure transcellular Cl -current across single layer FRT cells and freshly isolated colon mucosa. A closed loop experiment to measure colon fluid secretion in vivo. Results: Anthraquinone compounds rhein, aloe-emodin and 1,8-dihydroxyanthraquinone (DHAN) stimulated I -influx through CFTR chloride channel in a dose-dependent manner in the presence of physiological concentration of cAMP. In the short-circuit current assay, the three compound enhanced Cl -currents in epithelia formed by CFTR-expressing FRT cells with EC 50 values of 73±1.4, 56±1.7, and 50±0.5 μmol/L, respectively, and Rhein also enhanced Cl -current in freshly isolated rat colonic mucosa with a similar potency. These effects were completely reversed by the CFTR selective blocker CFTR inh -172. In in vivo closed loop experiments, rhein 2 mmol/L stimulated colonic fluid accumulation that was largely blocked by CFTR inh -172. The anthraquinone compounds did not elevate cAMP level in cultured FRT cells and rat colonic mucosa, suggesting a direct effect on CFTR activity. Conclusion: Natural anthraquinone compounds in vegetable laxative drugs are CFTR potentiators that stimulated colonic chloride and fluid secretion. Thus CFTR chloride channel is a molecular target of vegetable laxative drugs.

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“…To cover the topics of channelopathies other than aquaporin and Cl -channels we extended the invitation to contribute papers from several leading scientists who did not attend the symposium. These articles in this special issue impart a summary of the recent advances in the study of molecular mechanisms and functional roles of a variety of ion channels including Na + [16] , K + [17][18][19][20] , Ca 2+ [21] , Cl - [22][23][24][25][26] ,…”