Role of the PI3/PKB signaling pathway in cAMP-mediated translocation of rat liver Ntcp

cAMP stimulates Na+-taurocholate (TC) cotransport by translocating the Na+- TC-cotransporting peptide (Ntcp) to the plasma membrane. The present study was undertaken to determine whether the phosphatidylinositol-3-kinase (PI3K )-signaling pathway is involved in cAMP-mediated translocation of Ntcp. The ability of cAMP to stimulate TC uptake declined significantly when hepatoc ytes were pretreated with PI3K inhibitors wortmannin or LY-294002. Wortmann in inhibited cAMP-mediated translocation of Ntcp to the plasma membrane, cA MP stimulated protein kinase B (PKB) activity by twofold within 5 min, an e ffect inhibited by wortmannin. Neither basal mitogen-activated protein kina se (MAPK) activity nor cAMP-mediated inhibition of MAPK activity was affect ed by wortmannin. cAMP also stimulated p70(S6K) activity. However, rapamyci n, an inhibitor of p70S6K, failed to inhibit cAMP-mediated stimulation of T C uptake, indicating that the effect of cAMP is not mediated via p70(S6K). Cytochalasin D, an inhibitor of actin filament formation, inhibited the abi lity of cAMP to stimulate TC uptake and Ntcp translocation. Together, these results suggest that the stimulation of TC uptake and Ntcp translocation b y cAMP may be mediated via the PI3K/PKB signaling pathway and requires inta ct actin filaments.