Regulation and translocation of ATP-dependent apical membrane proteins in rat liver.
The bile canalicular membrane contains four specific ATP-dependent transport processes that are involved in secretion of bile acids, non-bile acid organic anions (mrp1), phospholipids (mdr2), and organic cations (mdr3). The aim of this study was to determine how the canalicular presence of these transport proteins is regulated. Canalicular membrane vesicles (CMV) were prepared from livers of rats treated with taurocholate (TC) and/or dibutyryl-adenosine 3',5'-cycle monophosphate (DBcAMP) with and without pretreatment with colchicine. Transport studies were performed with radiolabeled substrates. Changes in the relative amounts of transport proteins were determined by Western blots. Compared with controls, the specific activity of each of the transport processes was enhanced 1.5- and 3-fold with TC and DBcAMP treatments, respectively. Western blots revealed the same increases with mdr2 and mdr3. Pretreatment of rats with colchicine prevented these responses fully with TC treatment, whereas only partial prevention was obtained with DBcAMP treatment. Besides the ATP-dependent transporters, the relative specific activities of the canalicular membrane ectoenzyme markers, leucine aminopeptidase and gamma-glutamyltranspeptidase, were also affected 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 in the relative amounts of these proteins in the membrane.
Gatmaitan
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Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Nies
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Arias
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D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001648:Bile Canaliculi / Q000201:enzymology / Q000378:metabolism; D001692:Biological Transport; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D011961:Receptors, Fc / Q000378:metabolism; D013656:Taurocholic Acid / Q000494:pharmacology
D002352:Carrier Proteins; C045281:IgA receptor; D008565:Membrane Proteins; D010743:Phospholipids; D011108:Polymers; D011961:Receptors, Fc; D013656:Taurocholic Acid; D003994:Bucladesine; D000255:Adenosine Triphosphate; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases