Hepatic secretion When patients with PBC are treated with UDCA, serum levels of bilirubin [216] and endogenous bile salts [230] decrease. This effect of UDCA seems to be mediated by posttranscriptional rather than transcriptional mechanisms, as mRNA levels of key transporters like the conjugate export pump, ABCC2/MRP2, and the bile salt export pump, ABCB11/BSEP, are not affected by UDCA in man. Enhanced hepatic protein levels of BSEP, but not MRP2, have been observed under UDCA treatment in patients with gallstones [228] and may contribute to improved elimination of bile salts [231] . In an animal model of cholestasis, UDCA increases the density of Bsep and Mrp2 in the canalicular membrane of the rat by stimulating transporter targeting and insertion into the membrane [232] by a cooperative protein kinase C α/protein kinase A-dependent mechanism [224, [233] [234] [235] . An integrin-dependent dual signaling pathway involving mitogen-activated protein kinases (MAPK) Erk 1/2 and p38 MAPK has been shown to mediate UDCA-induced canalicular BSEP insertion in normal [236, 237] , but not cholestatic [238] hepatocytes. Whether UDCA-induced kinase-mediated phosphorylation of carriers contributes to enhanced canalicular transporter density and activity needs to be studied in more detail [224, 235, 239] .