What we have learned about bumetanide and the concept of multispecific bile acid/drug transporters from the liver

• Published in: Journal of hepatology Vol. 24 Suppl 1; pp. 42 - 46
• Main Authors: Petzinger, E, Blumrich, M, Brühl, B, Eckhardt, U, Föllmann, W, Honscha, W, Horz, J A, Müller, N, Nickau, L, Ottallah-Kolac, M, Platte, H D, Schenk, A, Schuh, K, Schulz, K, Schulz, S
• Format: Journal Article
• Language: English
• Published: Netherlands 1996
• Subjects: Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - metabolism; Bile Acids and Salts - metabolism; Bumetanide - metabolism; Carrier Proteins - metabolism; Drug Carriers - metabolism; Humans; Liver - metabolism; Male; Sodium-Potassium-Chloride Symporters
• ISSN: 0168-8278

Bumetanide is a weak organic acid which is transported into hepatocytes by a transport system that is related neither to the cloned sodium-dependent taurocholate cotransporting polypeptide Ntcp nor to the cloned organic anion transporting polypeptide oatp. Bumetanide is known to be transported in the kidney by a multispecific organic anion transporter which is the pAH-transporter from the proximal tubule cell. In the liver, bumetanide uptake competes with bile acid uptake, indicating a functionally related multispecific transporter for bile acids and drugs in hepatocytes. This multispecific bile acid transporter MBAT has not been cloned yet. When basolateral membranes were photoaffinity labeled with [3H]bumetanide, several bumetanide binding proteins were separated and identified after protein sequencing from two-dimensional electrophoresis gels.