Effect of Huoxiang-zhengqi liquid on HCO(3)(-) secretion by intact porcine distal airway epithelium.
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) μA/cm(2), 16.6% and 62.7% of which was inhibited by amiloride (epithelial Na(+) channel blocker, 100 μmol/L) and NPPB (cystic fibrosis transmembrane conductance regulator Cl(-) channel blocker, 100 μmol/L). Substitution of Cl(-) with impermeable gluconate(-) in the K-H bath solution resulted in a basal current of (54.0±6.7) μA/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 μmol/L/100 μmol/L) stimulated an increase of (13.8±1.9) μA/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) μA/cm(2) in HCO(3)(-)-dependent, DPC-inhibitable I(SC) (I(HCO(3))). Noticeably, basolateral application of HZL (10 μL/mL) in normal K-H solution evoked an I(SC) of (15.9±2.4) μA/cm(2). The EC(50) of this I(SC) was (6.1±1.4) μL/mL. When substituting Cl(-), HZL stimulated an increase of (7.4±1.9) μA/cm(2) in I(HCO(3)), suggesting HZL-induced 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) μA/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.
Xie
Chen
C
Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China.
Wang
Xiao-Fei
XF
Qi
Xiu-Juan
XJ
Lu
Li-Li
LL
Chan
Hsiao-Chang
HC
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism; D013552:Swine
D001639:Bicarbonates; D004365:Drugs, Chinese Herbal; C516480:Huoxiang-zhengqi; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D000584:Amiloride