title: Bak Foong Pills stimulate anion secretion across normal and cystic fibrosis pancreatic duct epithelia.
abstract: The present study examined the effect of Bak Foong Pills (BFP), an over-the-counter traditional Chinese medicine (China registration no. Z980035), on anion secretion and the underlying signaling pathways in normal and cystic fibrosis pancreatic duct cell lines, CAPAN-1 and CFPAC-1, respectively, using the short-circuit current technique. Apical addition of BFP ethanol extract (600 microg/ml) induced a fast transient I(SC) peak that was followed by a slower but more sustained increase in I(SC) in CAPAN-1 cells. However, the response to BFP in CFPAC-1 was predominantly the first transient peak. Apical addition of DIDS (200 microM) inhibited the first peak by more than 60% in both cell lines without significantly affecting the second I(SC) rise. More than 85% of the BFP-induced first transient in both cell lines was inhibited when extra and intracellular Ca(2+) was chelated or emptied by pre-treatment with BAPTA (100 microM) and thapsigargin (10 microM), respectively. Acute addition of PMA (1 microM), a PKC activator, blocked more than 95% of the BFP-induced first peak in both cell lines, consistent with previously reported PKC modulation of Ca(2+)-dependent pancreatic anion secretion. The BFP-induced second I(SC) rise in CAPAN-1 could be inhibited by 73.6% and 71.13% by pretreatment of the cells with MDL-12330A (20 microM), an adenylate cyclase inhibitor and Rp-cAMP (200 microM), a cyclic AMP antagonist, respectively. However, less than 25% of the I(SC) was inhibited by combined treatment with BAPTA and thapsigargin. The second rise was also completely blocked by DPC (2mM) or Glibenclamide (1mM). The results indicate that BFP ethanol extract stimulates pancreatic duct anion secretion in normal and CF cells via different signaling pathways involving both Ca(2+) and cAMP.
authors.affiliation: Epithelial Cell Biology Research Center, Department of Physiology, The Chinese University of Hong Kong, Shatin, NT, PR China.
authors.forename: Jin Xia
authors.initials: JX
authors.lastname: Zhu
authors.forename: Pui Shan
authors.initials: PS
authors.lastname: Lo
authors.forename: Wen Chao
authors.initials: WC
authors.lastname: Zhao
authors.forename: Ning
authors.initials: N
authors.lastname: Tang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Dewi K
authors.initials: DK
authors.lastname: Rowlands
authors.forename: Yu Lin
authors.initials: YL
authors.lastname: Gou
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Chung
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000838:Anions / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003550:Cystic Fibrosis / Q000503:physiopathology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013607:Tablets
chemical_list: D000838:Anions; C508116:Bak Foong Pills; D004365:Drugs, Chinese Herbal; D013607:Tablets; D000242:Cyclic AMP; D002118:Calcium