title: Regulation of taurocholate transport in freshly isolated proximal tubular cells of the rat kidney by protein kinases.
abstract: OBJECTIVE
  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 3H-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 3H-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 3H-taurocholate uptake. Phorbol myristate acetate and dioctanolglycerol, activators of PKC, and chelerythrine, a selective inhibitor of PKC, did not affect 3H-taurocholate uptake. Likewise the phosphatidylinositol-3 kinase inhibitor wortmannin and the tyrosine kinase inhibitor genistein induced no significant change of cellular 3H-taurocholate uptake. In a sodium-free medium forskolin and PD98059 did not affect 3H-taurocholate uptake but SB203580 significantly decreased it.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Toxicology, Aachen University, Aachen, Germany.
authors.forename: Jan Henrik
authors.initials: JH
authors.lastname: Schlattjan
authors.forename: Susanne
authors.initials: S
authors.lastname: Benger
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrler
authors.forename: Ulrike
authors.initials: U
authors.lastname: von Rango
authors.forename: Joachim
authors.initials: J
authors.lastname: Greven
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002478:Cells, Cultured; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D013656:Taurocholic Acid / Q000493:pharmacokinetics*
chemical_list: D013656:Taurocholic Acid; D011494:Protein Kinases