Ginkgolide C Stimulates CFTR-mediate Anion Conductance in Distal Colon: Implication for Therapy of Gastrointestinal Diseases

Chemical Research in Chinese Universities ›› 2009, Vol. 25 ›› Issue (6): 909-913.

• Articles • Previous Articles Next Articles

Ginkgolide C Stimulates CFTR-mediate Anion Conductance in Distal Colon: Implication for Therapy of Gastrointestinal Diseases

LIAO Qi^1,2, MA Xiao-yan^1*, WU Fu-ju¹, YANG Li-xiao¹ and WANG Shuai¹

1. Second Teaching Hospital of Jilin University, Changchun 130041, P. R. China;
2. The Daqing Longnan Hospital, Daqing 163453, P. R. China

Received:2009-01-19 Revised:2009-04-07 Online:2009-11-25 Published:2010-01-25
Contact: MA Xiao-yan. E-mail: mxytheblessed@sina.com
Supported by:
Supported by Changchun?Municipal?Science?and?Technology?Fund(No.2008116), Science and Technology Fund of Jilin Province(No.20090464).

Abstract

Abstract:

The effects and the mechanisms of natural compounds ginkgolides on CFTR-mediate anion transport were investigated. The CFTR-mediate iodide influx rates were studied via a cell-based fluorescence assay done for FRT cells stably transfected by CFTR; transepithelial short-circuit current recordings of FRT cells and rat distal colon mucosa were respectively obtained. Cellular cAMP concentrations were measured via a radioimmunoassay analysis kit. Ginkgolide C dose-dependently increases CFTR-mediate anion transport, whereas ginkgolide A and B show no effect. The activation is sensitive to CFTR specific activator CFTR_inh-172. Ginkgolide C stimulated amiloride and indomethacin pre-treated Cl^- currents in rat distal colon mucosa. Studies on FRT cells also manifest that ginkgolide C had additive effect with FSK/IBMX mixture and didn’t elevate intracellular cAMP concentration, which implies it works through a direct binding mechanism. In conclusion, Ginkgolide C directly stimulates CFTR-mediate anion transport. Ginkgolide C may be a promising drug for the prevention and treatment of CFTR-related diseases such as idiopathic chronic pancreatitis(ICP), habitual constipation, and keratoconjunctivitis sicca(KCS).

Key words: Ginkgolide; Cystic fibrosis transmembrane conductance regulator; Fluorescence; Mucosa

LIAO Qi, MA Xiao-yan*, WU Fu-ju, YANG Li-xiao and WANG Shuai. Ginkgolide C Stimulates CFTR-mediate Anion Conductance in Distal Colon: Implication for Therapy of Gastrointestinal Diseases[J]. Chemical Research in Chinese Universities, 2009, 25(6): 909-913.

References

[1] Riordan J. R., Rommens J. M., Kerem D., et al., Science, 1989, 245, 1066
[2] Gregory R. J., Cheng S. H., Rich D. P., et al., Nature, 1990, 347, 382
[3] Kerem B., Rommens K. M., Buchanan D., et al., Science, 1989, 245, 1073
[4] Gabriel S. E., Brigman K. N., Koller B. H., et al., Science, 1994, 266, 107
[5] Chao A. C., de Sauvage F. J., Dong Y. J., et al., EMBO J., 1994, 13, 1065
[6] Kimberg D. V., Field M., Johnson J., et al., J. Clin. Invest., 1971, 50, 1218
[7] Ma T., Thiagarajah J. R., Yang H., et al., J. Clin. Invest., 2002 , 110, 1651
[8] Cohn J. A., J. Clin. Gastroenterol., 2005, 39, S70
[9] Tariq S. H., J. Am. Med. Dir. Assoc., 2007, 8, 209
[10] Boonkaew T., Camper N. D., Phytomedicine, 2005, 12, 318
[11] Yoshikawa T., Naito Y., Kondo M., Antioxid. Redox. Signal., 1999, 1, 469
[12] Sierpina V. S., Wollschlaeger B., Blumenthal M., Am. Fam. Physician., 2003, 68, 923
[13] Thiagarajah J. R., Verkman A. S., Trends Pharmacol. Sci., 2005, 26, 172
[14] Thiagarajah J. R., Verkman A. S., Curr., Opin. Pharmacol., 2003, 3, 594
[15] Lundgren O., harmacol. Toxicol., 2002, 90, 109
[16] Farthing M. J., Gut, 2002, 50, III15
[17] Al-Awqati Q., J. Clin. Invest., 2002, 110, 1599
[18] Galietta L.V., Jayaraman S., Verkman A. S., Am. J. Physiol. Cell Physiol., 2001, 281, C1734
[19] Ma T., Vetrivel L., Yang H., J. Biol. Chem., 2002, 277, 37235
[20] He Q., Zhu J. X., Xing Y., et al., World J. Gastroenterol., 2005, 11, 4173
[21] Hwang T. C., Sheppard D. N., Trends. Pharmacol. Science, 1999, 20, 448
[22] Derand R., Bulteau-Pignoux L., Becq F., J. Biol. Chem., 2002, 277, 35999
[23] Dalemans W., Barbry P., Champigny G., et al., Nature, 1991, 354, 526
[24] Denning G. M., Anderson M. P., Amara J. F., et al., Nature, 1992, 358, 761
[25] Kopito R. R., Physiol. Rev., 1999, 79, S167
[26] Ewe K., Pharmacology, 1988, 36, 73
[27] Keely S. J., Barrett K. E., Ann. N. Y., Acad. Sci., 2000, 915, 67
[28] Barrett K. E., Keely S. J., Annu. Rev. Physiol., 2000, 62, 535
[29] Lundgren O., Pharmacol. Toxicol., 2002, 90, 109
[30] Lundgren O., Gastroenterology, 1998, 115, 1009

Ginkgolide C Stimulates CFTR-mediate Anion Conductance in Distal Colon: Implication for Therapy of Gastrointestinal Diseases

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 0

Recommended Articles

Metrics

Comments