Background/Aims: The bile acids filtered through the glomeruli nearly completely escape urinary excretion due to an efficient tubular reabsorption process. Reabsorption is mediated mainly by the sodium-dependent bile acid transporter (ASBT) which is located in the brush border membranes of proximal tubular cells. The present study addresses the question whether this transporter is subject to short-term regulation by protein kinases. Methods: The effects of specific activators or inhibitors of eight different protein kinases (PKs) on <sup>3</sup>H-taurocholate uptake of proximal tubular cells were investigated. The cells were freshly isolated from rat kidneys by nycodenz density gradient centrifugation. Results: Activation of the cAMP/PKA system by forskolin, 8-Br-cAMP, or the cAMP phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine significantly diminished cellular <sup>3</sup>H-taurocholate uptake whereas 8-Br-cGMP had no effect. Also the MEK1/2 inhibitors PD98059 and U0126, and the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 decreased <sup>3</sup>H-taurocholate uptake. Phorbol myristate acetate and dioctanolglycerol, activators of PKC, and chelerythrine, a selective inhibitor of PKC, did not affect <sup>3</sup>H-taurocholate uptake. Likewise the phosphatidylinositol-3 kinase inhibitor wortmannin and the tyrosine kinase inhibitor genistein induced no significant change of cellular <sup>3</sup>H-taurocholate uptake. In a sodium-free medium forskolin and PD98059 did not affect <sup>3</sup>H-taurocholate uptake but SB203580 significantly decreased it. Conclusion: It is concluded that PKA and MAP kinases are involved in the regulation of the ASBT-mediated taurocholate uptake into proximal tubular cells. p38 MAP kinase may have an additional effect on a sodium-independent tubular taurocholate transporter.