title: Effect of sodium ferulate on human colonic anion secretion and the underlying signaling mechanism.
abstract: The present study investigated the effect of ferulic acid, a compound purified from traditional Chinese herbal medicine Chuanxiong and Awei, on anion secretion by human colonic cells (T84) using the short circuit current (I(SC)) and microspectrofluorimetric technique. Basolateral administration of sodium ferulate (SF) produced a concentration-dependent increase of I(SC) in T84 cells with an EC50 of 1.2 mM. The SF-induced increase in I(SC) contained a transient peak followed by a sustained plateau. Removal of extracellular Cl-, basolateral addition of bumetanide, an inhibitor of the Na+ - K+ - Cl- cotransporter (NKCC) and apical pretreatment with DPC, a Cl- channels blocker, decreased the SF-induced increase in I(SC) by 94% (p < 0.001), 84% (p < 0.001) and 85% (p < 0.001) respectively. Pretreatment with thapsigargin, a specific microsomal Ca2+-ATPase inhibitor, in combination with EGTA, a Ca2+ chelator, decreased the SF-induced peak by 52% (p < 0.01) and inhibited the SF-induced plateau by 60% (p < 0.05). Pretreatment with MDL12330A, an adenylate cyclase inhibitor, blocked the SF-induced I(SC) plateau by 87% (p < 0.01) but did not affect the SF-induced I(SC) peak. Microspectrofluorimetric measurements show that SF induced a sustained increase in [Ca2+]i. The results suggested that SF could induce Cl- secretion in T84 cells via Ca2+ and cAMP-dependent pathways.
authors.affiliation: Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Wen Chao
authors.initials: WC
authors.lastname: Zhao
authors.forename: Jin Xia
authors.initials: JX
authors.lastname: Zhu
authors.forename: Gui Hong
authors.initials: GH
authors.lastname: Zhang
authors.forename: Connie Hau Yan
authors.initials: CH
authors.lastname: Wong
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Chung
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003373:Coumaric Acids / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects*; D049994:Sodium Potassium Chloride Symporter Inhibitors; D064506:Solute Carrier Family 12, Member 2; D013050:Spectrometry, Fluorescence
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D002712:Chlorides; D003373:Coumaric Acids; D004791:Enzyme Inhibitors; C578877:SLC12A2 protein, human; D049994:Sodium Potassium Chloride Symporter Inhibitors; D064506:Solute Carrier Family 12, Member 2; C004999:ferulic acid; D000242:Cyclic AMP; D002118:Calcium