Regulation of hepatic transport systems involved in bile secretion during liver regeneration in rats

We investigated the expression of hepatic transport systems involved in bil e secretion during liver regeneration after partial hepatectomy (PH) in rat s. Initial studies showed maximal BrdU incorporation 24 hours after PH. The refore, transporter expression and bile secretion were analyzed in detail a t this time. The mRNA levels of the multidrug resistance genes mdr1a and mr p1 slightly increased, whereas mdr1b mRNA levels showed an extensive increa se after PH. The mRNA levels of the conjugate transporter, mrp2, decreased slightly, whereas mrp2 protein levels did not change. Bilirubin secretion d id not change, but the biliary glutathione secretion markedly decreased and the hepatic GSH content increased. The messenger RNA levels of the bile sa lt uptake transporters ntcp, oatp1, and oatp2 and the bile salt exporter, b sep/spgp, all decreased with ntcp showing the most prominent decrease. Prot ein levels of ntcp dramatically decreased whereas oatp2 only slightly decre ased. Oatp1 protein expression slightly increased and bsep/spgp protein lev els did not change. Decreased levels of bile salt uptake systems were assoc iated with a 10-fold increase in the plasma bile salt concentration, yet, b ile flow and bile salt secretion were increased when expressed per gram liv er and unaffected when expressed on the basis of body weight. In conclusion , during the initial phase of rat liver regeneration ntcp is down-regulated whereas other transporter proteins involved in bile secretion are only sli ghtly affected. Despite increased serum bile salt levels the remnant liver is not cholestatic: bile flow is maintained by uptake of bile salts probabl y via oatp isoforms and their secretion via bsep/ spgp.