Basic Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2005; 11(27): 4173-4179
Published online Jul 21, 2005. doi: 10.3748/wjg.v11.i27.4173
Tetramethylpyrazine stimulates cystic fibrosis transmembrane conductance regulator-mediated anion secretion in distal colon of rodents
Qiong He, Jin-Xia Zhu, Ying Xing, Lai-Ling Tsang, Ning Yang, Dewi Kenneth Rowlands, Yiu-Wa Chung, Hsiao-Chang Chan
Qiong He, Jin-Xia Zhu, Ying Xing, Ning Yang, Department of Physiology, Medical School, Zhengzhou University, Zhengzhou 450052, Henan Province, China
Qiong He, Jin-Xia Zhu, Lai-Ling Tsang, Ning Yang, Dewi Kenneth Rowlands, Yiu-Wa Chung, Hsiao-Chang Chan, Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Author contributions: All authors contributed equally to the work.
Supported by the Innovation and Technology Fund of Hong Kong, China
Correspondence to: Dr. Hsiao-Chang Chan, Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. hsiaochan@cuhk.edu.hk
Telephone: +852-2609-6839 Fax: +852-2603-5022
Received: August 19, 2004
Revised: October 1, 2004
Accepted: October 5, 2004
Published online: July 21, 2005
Abstract

AIM: To investigate the effect of tetramethylpyrazine (TMP), an active compound from Ligustium Wollichii Franchat, on electrolyte transport across the distal colon of rodents and the mechanism involved

METHODS: The short-circuit current (ISC) technique in conjunction with pharmacological agents and specific inhibitors were used in analyzing the electrolyte transport across the distal colon of rodents. The underlying cellular signaling mechanism was investigated by radioimmunoassay analysis (RIA) and a special mouse model of cystic fibrosis.

RESULTS: TMP stimulated a concentration-dependent rise in ISC, which was dependent on both Cl- and HCO3-, and inhibited by apical application of diphenylamine-2,2’-dicarboxylic acid (DPC) and glibenclamide, but resistant to 4,4’-diisothiocyanatostilbene-2,2’-disulfonic acid disodium salt hydrate (DIDS). Removal of Na+ from basolateral solution almost completely abolished the ISC response to TMP, but it was insensitive to apical Na+ replacement or apical Na+ channel blocker, amiloride. Pretreatment of colonic mucosa with BAPTA-AM, a membrane-permeable selective Ca2+ chelator, did not significantly alter the TMP-induced ISC. No additive effect of forskolin and 3-isobutyl-1-methylxanthine (IBMX) was observed on the TMP-induced ISC, but it was significantly reduced by a protein kinase A inhibitor, H89. RIA results showed that TMP (1 mmol/L) elicited a significant increase in cellular cAMP production, which was similar to that elicited by the adenylate cyclase activator, forskolin (10 µmol/L). The TMP-elicited ISC as well as forskolin- or IBMX-induced ISC were abolished in mice with homozygous mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) presenting defective CFTR functions and secretions.

CONCLUSION: TMP may stimulate cAMP-dependent and CFTR-mediated Cl- and HCO3- secretion. This may have implications in the future development of alternative treatment for constipation.

Keywords: Tetramethylpyrazine, Ligustrazine, Colonic mucosa, Cl-, HCO3-, cAMP, CF mice