85 4% were female, w,,h a mean age afpresentatmn of 50 3 years. compared to 37 7 years for the males (pi0 05) Prerentmg complaints were ,a”ndtce m 50 5%. malaise and anhral@a m 23 3% whilst 26 2% were d&nosed after the findmn ofelevation of semm tmnsammase
2P
was ;a ~&gate the molecular mechanisms involved m the chalo~ctic effect of GL GL and 11s metabohtes were present, by HPLC, m m~cromolar amounts m bile collected from teolated rat lwrr perfused wth 100 M GL, but not I” the o~ematanl of normal rat cholangmcyte monolaycrs (NRC-I) exposed to 100 M GL on the basolateral vde. mdxating that cholcresn I” the isolated rat btle duct “mts (IBDU) IS “at due to GL nms”oll bv btle duct cells. GL-Induced cholanmocvte secretion (video-optical rrlammelry) uas ;“h,hn-ed by Cl- channel blockers, but not b; o,&nion ofHC03 Soi the &f”sion media suggesfmg 11s dependence on Cl- channels, hut not on Cl-t’HCO3exchanger By RTPCR the sulfonylurea receptor SUR-2B mRNA was expressed I” cholangiocytes. GL effects were tmmicked by tolbutamnde and mhthlted by dmzoxlde. GL-stmtulated secreton m lBDU was significantly Inhjblted hy p-glycoprotems mhlhltorn (verapamd and OF1209 18) and by tamox~fene. an mhtheor of a mdrl-hke protem, that m pancreatic CCIIS, couples SUR to granular Cl- channels (PNAS ‘55539.1999). Finally, CL chalerws UBF mhthaed by wonhmannm. LY294002, colchxinr, but “of by lumicolchlcme Tixse findmgs s”ggest that, aulfonylurras mtrractmg with the SUR receptor may promute sxocytuua I” chobmpmcytes by a mechanism involvmg mdr-like protems and Ci- transport