title: CFTR chloride channel as a molecular target of anthraquinone compounds in herbal laxatives.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: School of Life Sciences, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian 116029, China. hyanglnnu@gmail.com
authors: Hong
authors: H
authors: Yang
authors: Li-na
authors: LN
authors: Xu
authors: Cheng-yan
authors: CY
authors: He
authors: Xin
authors: X
authors: Liu
authors: Rou-yu
authors: RY
authors: Fang
authors: Tong-hui
authors: TH
authors: Ma
references: Pharmacology. 1988;36 Suppl 1:104-10
references: 3368508
references: Pflugers Arch. 2004 Oct;449(1):88-95
references: 15290302
references: J Cell Biol. 1992 Jun;117(6):1197-1209
references: 1318883
references: Am J Physiol. 1994 Apr;266(4 Pt 1):L405-13
references: 7513963
references: J Gen Physiol. 1977 Nov;70(5):635-60
references: 201723
references: Am J Physiol. 1992 Sep;263(3 Pt 1):C607-15
references: 1329520
references: Physiol Rev. 1999 Jan;79(1 Suppl):S23-45
references: 9922375
references: J Pharm Pharmacol. 1986 Aug;38(8):606-10
references: 2876077
references: Pharmacology. 1988;36 Suppl 1:31-9
references: 3368524
references: J Clin Invest. 1994 Jan;93(1):347-54
references: 7506713
references: J Biol Chem. 2002 Oct 4;277(40):37235-41
references: 12161441
references: World J Gastroenterol. 2005 Jul 21;11(27):4173-9
references: 16015685
references: J Endocrinol. 1996 Dec;151(3):431-7
references: 8994388
references: J Med Microbiol. 1998 Feb;47(2):151-7
references: 9879958
references: Aliment Pharmacol Ther. 1999 Apr;13(4):443-52
references: 10215727
references: J Clin Invest. 2002 Dec;110(11):1651-8
references: 12464670
references: Am J Physiol Cell Physiol. 2001 Nov;281(5):C1734-42
references: 11600438
references: Pharmacology. 1988;36 Suppl 1:111-9
references: 3368509
references: Pharmacology. 1988;36 Suppl 1:73-84
references: 2897128
references: Am Fam Physician. 2006 Feb 1;73(3):469-77
references: 16477894
references: Pharmacology. 1988;36 Suppl 1:40-8
references: 3368525
references: Gastroenterology. 2004 Feb;126(2):511-9
references: 14762788
references: Am J Physiol. 1998 Dec;275(6):G1274-81
references: 9843763
references: Nat Rev Drug Discov. 2009 Feb;8(2):153-71
references: 19153558
references: J Pharmacol Exp Ther. 2008 Apr;325(1):256-66
references: 18187619
references: Pharmacology. 1993 Oct;47 Suppl 1:86-97
references: 8234447