Effect of organic anions and taurolithocholate-3-sulfate on biliary excretion of temocapril in the rat

Abstract

Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, canalicular multispecific organic anion transporter/multidrug resistance protein 2. On the other hand, a multiplicity of canalicular organic anion transporter has been suggested. To examine the substrate specificity of canalicular multispecific organic anion transporter, we examined the effect of organic anions and lithocholate-3-sulfate on biliary excretion of temocapril, a prodrug of an angiotensin-converting enzyme inhibitor, temocaprilat, in rats. Biliary excretion of temocapril was delayed in EHBR. Biliary excretion of temocapril was inhibited by sulfobromophthalein and taurolichocholate-3-sulfate, but was not inhibited by phenolphthalein glucuronide. These findings further support the multiplicity of canalicular organic anion transporter, and in spite of a glucuronide conjugate phenolphthalein glucuronide seems too hydrophobic to be a good substrate of canalicular multispecific organic anion transporter.