Hepatic extraction of organic anions in the rat depends on ligand hydrophobicity
Hironori Tokumo
Gastrointestinal Research Unit, Research Institute and Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195–5218
Search for more papers by this authorNankei Aoyama
Gastrointestinal Research Unit, Research Institute and Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195–5218
Search for more papers by this authorNorbert Busch
Gastrointestinal Research Unit, Research Institute and Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195–5218
Search for more papers by this authorDaniel J. Mancuso
Gastrointestinal Research Unit, Research Institute and Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195–5218
Search for more papers by this authorCorresponding Author
R. Holzbach Thomas
Gastrointestinal Research Unit, Research Institute and Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195–5218
Gastrointestinal Research Unit, Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, Cleveland, OH 44195–5218===Search for more papers by this authorHironori Tokumo
Gastrointestinal Research Unit, Research Institute and Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195–5218
Search for more papers by this authorNankei Aoyama
Gastrointestinal Research Unit, Research Institute and Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195–5218
Search for more papers by this authorNorbert Busch
Gastrointestinal Research Unit, Research Institute and Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195–5218
Search for more papers by this authorDaniel J. Mancuso
Gastrointestinal Research Unit, Research Institute and Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195–5218
Search for more papers by this authorCorresponding Author
R. Holzbach Thomas
Gastrointestinal Research Unit, Research Institute and Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195–5218
Gastrointestinal Research Unit, Cleveland Clinic Foundation, One Clinic Center, 9500 Euclid Avenue, Cleveland, OH 44195–5218===Search for more papers by this authorAbstract
Non-bile-salt cholephilic organic anions are efficiently taken up by the liver. Recent work from our group has suggested the possible importance of relative hydrophobicity among various organic anions in hepatic uptake. To further validate and clarify this, we studied hepatic extraction of five different cholephilic dyes using the isolated perfused rat liver in single-pass mode. Albumin binding affinities and capacities for each of the ligands were measured in vitro to permit evaluation of in vivo interactions for each of them over a spectrum of unbound ligand concentrations. As expected, a strong positive correlation was found between ligand hydrophobicity and the relative degree of albumin binding affinity and capacity. Using appropriate experimental conditions, we also found a strong positive correlation between hepatic extraction efficiency for a given ligand and both its hydrophobicity and its unbound concentration. These data indicate that where the unbound ligand concentration is significant, the greater the ligand hydrophobicity, the greater is its efficiency of hepatic extraction. We conclude that hepatic extraction efficiency for non-bile-salt cholephilic organic anions depends on a combination of ligand hydrophilic/hydrophobic balance and the availability of the unbound ligand for uptake. (HEPATOLOGY 1991;13:62–67).
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