What we have learned about bumetanide and the concept of multispecific bile acid/drug transporters from the liver.
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.
Petzinger
E
E
Institute of Pharmacology and Toxicology, Justus Liebig University Giessen, Germany.
Blumrich
M
M
Brühl
B
B
Eckhardt
U
U
Föllmann
W
W
Honscha
W
W
Horz
J A
JA
Müller
N
N
Nickau
L
L
Ottallah-Kolac
M
M
Platte
H D
HD
Schenk
A
A
Schuh
K
K
Schulz
K
K
Schulz
S
S
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D002034:Bumetanide / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004337:Drug Carriers / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D028021:Sodium-Potassium-Chloride Symporters
D001647:Bile Acids and Salts; D002352:Carrier Proteins; D004337:Drug Carriers; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate