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Species Differences in the Distribution of Drug-Metabolizing Enzymes in the Pancreas

UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, Department of Surgery, Rheinische Friedrich-Wilhelms-University, Bonn, Germany

Jens Standop

UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, Department of Surgery, Rheinische Friedrich-Wilhelms-University, Bonn, Germany

Bruno M. Schmied

UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, Department of Visceral and Transplantation Surgery, Insel Hospital, Bern, Switzerland

Matthias B. Schneider

UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, Department of Visceral and Transplantation Surgery, Insel Hospital, Bern, Switzerland

Terence A. Lawson

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska

Parviz M. Pour

UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, ppour{at}unmc.edu., Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska

We investigated the cellular expression of 9 cytochrome P450-isozymes (CYP1A1, CYP1A2, CYP2B6, CYP2C8,9,19, CYP2D1, CYP2E1, CYP3A1, CYP3A2, CYP3A4) and 3 glutathione S-transferase-isozymes (GST- , GST-, GST-µ ) in the pancreas of hamsters, mice, rats, rabbits, pigs, dogs and monkeys, and in comparison with the human pancreas. A wide variation was found in the cellular localization of these enzymes between the 8 species. Most enzymes were expressed in the pancreas of the hamster, mouse, monkey and human, whereas rats, pigs, rabbits and dogs were lacking several isozymes. However, in all of the species the islet cells expressed more enzymes than ductal and acinar cells. An exclusive expression of enzymes in the islet cells was found in the hamster (CYP2E1), mouse (CYP1A1, CYP1A2, GST-, GST-µ ), rat (CYP2C8,9,19), rabbit (CYP1A2, CYP2B6, GST-), and pig (CYP1A1). Although no polymorphism was found in the pancreas of animals, in human tissue four enzymes were missing in about 50% of the cases. The results imply a greater importance of the islet cells in the metabolism of xenobiotics within the pancreas. The differences in the distribution of these drug-metabolizing enzymes in the pancreas between the species call for caution when extrapolating experimental results to humans.

Key Words: Drug-metabolizing enzymes • cytochrome P450 • glutathione S-transferase • laboratory animals.

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