REGULATION AND TRANSLOCATION OF ATP-DEPENDENT APICAL MEMBRANE-PROTEINS IN RAT-LIVER

The bile canalicular membrane contains four specific ATP-dependent tra nsport processes that are involved in secretion of bile acids, non-bil e acid organic anions (mrp1), phospholipids (mdr2), and organic cation s (mdr3). The aim of this study was to determine how the canalicular p resence of these transport proteins is regulated. Canalicular membrane vesicles (CMV) were prepared from livers of rats treated with tauroch olate (TC) and/or dibutyryl-adenosine 3',5'-cyclic monophosphate (DBcA MP) with and without pretreatment with colchicine. Transport studies w ere performed with radiolabeled substrates. Changes in the relative am ounts of transport proteins were determined by Western blots. Compared with controls, the specific activity of each of the transport process es was enhanced 1.5; and 3-fold with TC and DBcAMP treatments, respect ively. Western blots revealed the same increases with mdr2 and mdr3. P retreatment of rats with colchicine prevented these responses fully wi th TC treatment, whereas only partial prevention was obtained with DBc AMP treatment. Besides the ATP-dependent transporters, the relative sp ecific activities of the canalicular membrane ectoenzyme markers, leuc ine aminopeptidase and gamma-glutamyltranspeptidase, were also affecte d the same way. These results suggest that TC and DBcAMP increase the specific activity of the canalicular ATP-dependent transport proteins and some canalicular membrane ectoenzymes by stimulating an increase i n the relative amounts of these proteins in the membrane.