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Effect of Huoxiang--zhengqi liquid on HCO_(3)~(-) secretion by intact porcine distal airway epithelium

Xie Chen, Wang Xiaofei, Qi Xiujuan, Lu Lili, Chen Xiaozhang

Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong.Hong Kong；China；The Affiliated Hospital of Medical College of Qingdao University.Qingdao 266003,Shandong

Abstract

The short-circuit current （I_(SC)） technique was used to examine the effects of cAMP-evoking agents, forskolin/IBMX, and a Chinese medicinal formula, Huoxiang-zhengqi liquid （HZL） on HCO_(3)~(-) secretion by intact porcine distal airway epithelium. The freshly isolated airway epithelial tissue displayed a transepithelial basal current of （94.9±8.2）#mu#A/cm~(2), 16.6% and 62.7% of which was inhibited by amiloride （epithelial Na~(+) channel blocker, 100 #mu#mol/L） and NPPB （cystic fibrosis transmembrane conductance regulator Cl~(-) channel blocker, 100 #mu#mol/L）. Substitution of Cl~(-) with impermeable gluconate~(-) in the K-H bath solution resulted in a basal current of （54.0±6.7）#mu#A/cm~(2), which could be abolished by further removal of HCO_(3)~(-) in the solution, indicating HCO_(3)~(-) secretion under unstimulated conditions. Application of forskolin/IBMX （10 #mu#mol/L/100 #mu#mol/L） stimulated an increase of （13.8±1.9）#mu#A/cm~(2) in I_(SC) which could be blocked by Cl~(-) channel inhibitor DPC. With Cl~(-) and Cl~(-)/HCO_(3)~(-) substitution, forskolin/IBMX evoked an increase of （7.3±0.5） #mu#A/cm~(2) in HCO_(3)~(-)-dependent, DPC-inhibitable I_(SC) （I_(HCO_(3))）. Noticeably, basolateral application of HZL （10#mu#L/mL） in normal K-H solution evoked an I_(SC) of （15.9±2.4）#mu#A/cm~(2). The EC_(50) of this I_(SC) was （6.1±1.4） #mu#L/mL. When substituting Cl~(-), HZL stimulated an increase of （7.4±1.9）#mu#A/cm~(2) in I_(HCO_(3)), suggesting HZL-induced I_(HCO_(3)) secretion. After pretreating the epithelial tissues with forskolin/IBMX in Cl~(-)-free K-H solution, HZL induced a further increase of （8.4±0.9）#mu#A/cm~(2) in I_(HCO_(3)), and pretreating tissues with HZL did not significantly affect the subsequent forskolin/IBMX-induced I_(HCO_(3)) response, indicating that HZL- and forskolin/IBMX-induced I_(HCO_(3)) responses appeared to be independent and be most likely mediated via different cellular mechanisms. Our results suggest that HCO_(3)~(-) can be secreted by porcine distal airway epithelium under unstimulated and stimulated conditions, and the stimulatory effect of HZL on HCO_(3)~(-) secretion in the distal airway epithelium shows HZL to be a hopeful new agonist for distal airway HCO_(3)~(-) secretion that could be of therapeutic significance.

Key words: ion transport;bicarbonate;cystic fibrosis transmembrane conductance regulator;airway

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Citing This Article：

Xie Chen, Wang Xiaofei, Qi Xiujuan, Lu Lili, Chen Xiaozhang. Effect of Huoxiang--zhengqi liquid on HCO_(3)~(-) secretion by intact porcine distal airway epithelium. Acta Physiol Sin 2008; 60 (1): 90-96 (in Chinese with English abstract).