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 hepatocyte s by a transport system that is related neither to the cloned sodium-d ependent taurocholate cotransporting polypeptide Ntcp nor to the clone d organic anion transporting polypeptide oatp. Bumetanide is known to be transported in the kidney by a multispecific organic anion transpor ter 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 dru gs in hepatocytes. This multispecific bile acid transporter MEAT has n ot been cloned yet. When basolateral membranes were photoaffinity labe led with [H-3]bumetanide, several bumetanide binding proteins were sep arated and identified after protein sequencing from two-dimensional el ectrophoresis gels. (C) European Association for the Study of the Live r.