Effect of sodium ferulate on human colonic anion secretion and the underlying signaling mechanism.
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.
Zhao
Wen Chao
WC
Epithelial Cell Biology Research Center, Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.
Zhu
Jin Xia
JX
Zhang
Gui Hong
GH
Wong
Connie Hau Yan
CH
Chung
Yiu Wa
YW
Chan
Hsiao Chang
HC
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
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