title: Rifampicin Induces Bicarbonate-Rich Choleresis in Rats: Involvement of Anion Exchanger 2.
abstract: OBJECTIVE
  Previous studies have shown that rifampicin induced choleresis, the mechanisms of which have not been described. The aim of this study was to investigate the mechanisms underlying in vivo rifampicin-induced choleresis.
  
  
  METHODS
  In one experimental set, rats were treated chronically with rifampicin on days 1, 3 and 7. Serum and biliary parameters were assayed, and mRNA and protein levels, as well as the locations of the hepatic export transporters were analyzed by real-time PCR, western blot and immunofluorescence. Ductular mass was evaluated immunohistochemically. In another experimental set, rats received an acute infusion of rifampicin. The amount of rifampicin in bile was detected using HPLC. Biliary parameters were monitored following intrabiliary retrograde fluxes of the Cl(-)/HCO3 (-) exchange inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) in the infused rats.
  
  
  RESULTS
  Biliary bicarbonate output increased in parallel to the augmented bile flow in response to rifampicin, and this effect was abolished with intrabiliary administration of DIDS, but not NPPB. The biliary secretion of rifampicin with increases in bile flow and biliary rifampicin in response to different infused doses of the antibiotic show no significant correlations. After rifampicin treatment, the expression level of anion exchanger 2 (AE2) increased, while the location of hepatic transporters did not change. However, RIF treatment did not increase ductular mass significantly.
  
  
  CONCLUSIONS
  These results indicate that the increase in bile flow induced by rifampicin is mainly due to increased HCO3 (-) excretion mediated by increased AE2 protein expression and activity.
authors: Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, Anhui Province, China. hide2002@163.com.
authors: Wei
authors: W
authors: Wang
authors: Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, Anhui Province, China. renxiaofei1980@126.com.
authors: Xiaofei
authors: X
authors: Ren
authors: Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, Anhui Province, China. wzcaiyi2015@163.com.
authors: Yi
authors: Y
authors: Cai
authors: Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, Anhui Province, China. chlhhome@163.com.
authors: Lihong
authors: L
authors: Chen
authors: Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, Anhui Province, China. zwp0202@163.com.
authors: Weiping
authors: W
authors: Zhang
authors: Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230022, Anhui Province, China. xujm1017@163.com.
authors: Jianming
authors: J
authors: Xu
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001646:Bile / Q000378:metabolism*; D001652:Bile Ducts / Q000187:drug effects* / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D008297:Male; D009579:Nitrobenzoates / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D002756:Cholagogues and Choleretics; D009579:Nitrobenzoates; D012333:RNA, Messenger; C579494:Slc4a2 protein, rat; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012293:Rifampin
keywords: Anion exchanger 2; Bile flow; HCO3 −; Rifampicin