ATP-dependent transport of amphiphilic cations across the hepatocyte canalicular membrane mediated by mdr1 P-glycoprotein

FEBS Lett. 1994 Apr 25;343(2):168-72. doi: 10.1016/0014-5793(94)80312-9.

Abstract

The ATP-dependent transport of the three 3H-labeled, amphiphilic cations quinidine, N-(n-pentyl)-quinidinium, and N-(4',4'-azo-n-pentyl)-21-deoxyajmalinium was studied in rat canalicular plasma membrane vesicles. N-Alkylation of quinidine with an n-pentyl residue resulted in a permanently charged cationic substrate for ATP-dependent transport which exhibited a 10-fold higher transport rate relative to quinidine. The Km value was 0.4 microM for N-(n-pentyl)-quinidinium and 5 microM for quinidine. The permanently cationic and photolabile derivative of ajmaline, N-(4',4'-azo-n-pentyl)-21-deoxyajmalinium, was also an efficient substrate and served to label canalicular membrane proteins with molecular masses of 143 kDa and 108 kDa. ATP-dependent transport of the permanently charged amphiphilic cations was inhibited by the P-glycoprotein inhibitors and substrates quinidine, verapamil, and daunorubicin. The data demonstrate that N-alkylation of quinidine and ajmaline results in most efficient substrates for mdr1 P-glycoprotein-mediated ATP-dependent transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Adenosine Triphosphate / metabolism
  • Affinity Labels
  • Animals
  • Biological Transport, Active
  • Carrier Proteins / metabolism*
  • Cations / metabolism*
  • Liver / cytology
  • Liver / metabolism*
  • Male
  • Membrane Glycoproteins / metabolism*
  • Membranes / metabolism
  • Rats
  • Rats, Wistar

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Affinity Labels
  • Carrier Proteins
  • Cations
  • Membrane Glycoproteins
  • Adenosine Triphosphate