Received for publication September 18, 2006.
Revised January 15, 2007.
Accepted for publication January 16, 2007.

Function of both sinusoidal and canalicular transporters controls the concentration of organic anions within hepatocytes

Abstract

We hypothesized that the function of both sinusoidal and canalicular transporters importantly controls the concentrations of organic anions within normal hepatocytes. Consequently, we investigated how acute transport regulation of the sinusoidal organic anion transporting polypeptides (Oatps) and the canalicular multidrug resistance associated protein 2 (Mrp2) determines the hepatic concentrations of the organic anion gadobenate dimeglumine (BOPTA) in rat livers. Livers were perfused with labeled BOPTA in different experimental settings that modify the function of Oatps and Mrp2 through the protein kinase C (PKC) pathway. Intrahepatic concentrations were continuously measured with a gamma probe placed above rat livers. Labeled BOPTA was also measured in perfusate and bile. We showed that when the function of Oatps and Mrp2 is modified in such a way that BOPTA entry and exit are similarly decreased, concentrations of organic anions within hepatocytes remain unaltered. When exit through Mrp2 is abolished, hepatic concentrations are high if entry through Oatps is only slightly decreased (livers without Mrp2 expression) or low if BOPTA uptake is more importantly decreased (livers perfused with a PKC activator). These results highlight that the function of both sinusoidal and canalicular transporters is important to determine the concentration of organic anions within hepatocytes.

Key words: Neuropeptides, Vasopressin/Oxytocin, Organic anion, Receptor-mediated