H. Takikawa et al., Effect of organic anions and taurolithocholate-3-sulfate on biliary excretion of temocapril in the rat, HEPATOL RES, 15(2), 1999, pp. 157-162
Biliary organic anion excretion is mediated by an ATP-dependent primary act
ive transporter, canalicular multispecific organic anion transporter/multid
rug resistance protein 2. On the other hand, a multiplicity of canalicular
organic anion transporter has been suggested. To examine the substrate spec
ificity of canalicular multispecific organic anion transporter, we examined
the effect of organic anions and lithocholate-3-sulfate on biliary excreti
on 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 t
aurolichocholate-3-sulfate, but was not inhibited by phenolphthalein glucur
onide. These findings further support the multiplicity of canalicular organ
ic anion transporter, and in spite of a glucuronide conjugate phenolphthale
in glucuronide seems too hydrophobic to be a good substrate of canalicular
multispecific organic anion transporter. (C) 1999 Elsevier Science Ireland
Ltd. All rights reserved.