Luteolin activates the cystic fibrosis transmembrane conductance regulator chloride channel

Abstract

Abstract: AIM: To investigate the activation effect of luteolin on cAMP-dependent cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. METHODS: A stable transfected epithelial cell line coexpression human CFTR and a green fluorescent protein mutant with ultra-high halide sensitivity (YFP-H148Q) were used to determine CFTR-mediated iodide influx rate. RESULTS: Luteolin increased dose-dependently CFTR-mediated iodide influx.The activity was rapid, reversible and Forskolin-dependent. Luteolin had additive effect with Forskolin mixture and did not elevate intracellular cAMP concentration wirhout Forskolin. CONCLUSION: The study identified luteolin could dose-dependently activate CFTR and provided that luteolin acted by combining with CFTR directly.

Key words: cystic fibrosis transmembrane conductance regulator, hypertension, Cl-transport, luteolin, activator

CLC Number:

R965.2

HOU Shu-guang, LIN Sen, YU Bo, JIN Ling-ling, YANG Hong. Luteolin activates the cystic fibrosis transmembrane conductance regulator chloride channel[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(3): 249-253.

References

[1] Riordan JR, Rommens JM, Kerem B, et al.Identification of the cystic fibrosis gene:cloning and characterization of complementary DNA[J].Science, 1989, 245(4922): 1066-1073
[2] Robert R, ThoreauV, Norez C, et al.Regulation of the cystic fibrosis transmembrane conductance regulator channel by β-adrenergic agonists and vasoactive intestinal peptide in rat smooth muscle cells and its role in vasotelaxation[J].J Biol Chem, 2004, 279(20):21160-21168
[3] RobertR, Norez C, Becq F.Disruption of CFTR chloride channel alters mechanical properties and cAMP-dependent Cl-transport of mouse aortic smooth muscle cells[J].J Hy siol, 2005, 568(2):483-495
[4] Ichimura T, Yamanaka A, Ichiba T, et al.Antihypertensive effect of an extract of Passiflora edulis rind in spontaneously hypertensive rats[J].Biosci Biotechnol Biochem, 2006, 70(3):718-721
[5] Jiang H, Xia Q, Wang X, et al.Luteolin induces vasorelaxion in rat thoracic aorta via calcium and potassium channels[J].Pharmazie, 2005, 60(6):444-447
[6] Duarte J, Perez Vizcaino F, Utrilla P, et al.Vasodilatory effects of flavonoids in rat aortic smooth muscle Structureactivity relationships[J].Gen Pharmacol, 1993, 24(4): 857-862
[7] Hwang TC, Wang F, Yang IC, et al.Genistein potentiates wild-type and delta F508-CFTR channel activity[J].Am J Physiol, 1997, 273(3 Pt 1):C988-998
[8] Galietta LV, Jayaraman S, Verkman AS.Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists[J].Am J Physiol Cell Physiol, 2001, 281(5):C1734-1742
[9] Ma T, Vetrivel L, Yang H, et al.High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening[J].J Biol Chem, 2002, 277(40):37235-37241
[10] Ma T, Thiagarajah JR, Yang H, et al.Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion[J]. J Clin Invest, 2002, 110(11):1651-1658
[11] Hwang TC, Sheppard DN.Molecular pharmacology of the CFTR Cl-channel[J].Trends Pharmacol Sci, 1999, 20(11):448-453
[12] Ajay M, Achike FI, Mustafa MR.Modulation of vascular reactivity in normal, hypertensive and diabetic rat aortae by a non-antioxidant flavonoid[J].Pharmacol Res, 2007, 55(5):385-391
[13] Yamamoto Y, Oue E.Antihypertensive effect of quercetin in rats fed with a high-fat high-sucrose diet[J].Biosci Biotechnol Biochem, 2006, 70(4):933-939
[14] Siriviriyakul P, Khemapech S, Monsiri K, et al.The vascular effect of genistein:what is its mechanism, nitric oxide or PGI2[J] ? Clin HemorheolMicrocirc, 2006,34(1-2):97-101
[15] Jeon SB, Kim G, Kim JI, et al.Flavone inhibits vascular contraction by decreasing phosphorylation of the myosin phosphatase target subunit[J].Clin Exp Pharmacol Physiol, 2007,34(11):1116-1120
[16] Ghayur MN, Khan H, Gilani AH.Antispasmodic, bronchodilator and vasodilator activities of (+)-catechin, a naturally occurring flavonoid[J].Arch Pharm Res, 2007,30(8):970-975
[17] Lemos VS, Cortes SF, dos Santos MH, et al.Structure and vasorelaxant activity of floranol, a flavonoid isolated from the roots of Dioclea grandiflora[J].Chem Biodivers, 2006,3(6):635-645.