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

Alexis B. Ulrich, Jens Standop, Bruno M. Schmied, Matthias B. Schneider, Terence A. Lawson, Parviz M. Pour

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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-π, GST-α, 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-α, GST-μ), rat (CYP2C8,9,19), rabbit (CYP1A2, CYP2B6, GST-π), 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.

Original languageEnglish (US)
Pages (from-to)247-253
Number of pages7
JournalToxicologic Pathology
Volume30
Issue number2
DOIs
StatePublished - Feb 2002

Fingerprint

Pancreas
Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP1A1
Enzymes
Islets of Langerhans
Cricetinae
Pharmaceutical Preparations
Isoenzymes
Rats
Cytochrome P-450 CYP2E1
Swine
Rabbits
Haplorhini
Dogs
Cytochrome P-450 CYP3A
Acinar Cells
Xenobiotics
Glutathione Transferase
Polymorphism
Metabolism

Keywords

  • Drug-metabolizing enzymes
  • cytochrome P450
  • glutathione S-transferase
  • laboratory animals

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

Cite this

Ulrich, A. B., Standop, J., Schmied, B. M., Schneider, M. B., Lawson, T. A., & Pour, P. M. (2002). Species Differences in the Distribution of Drug-Metabolizing Enzymes in the Pancreas. Toxicologic Pathology, 30(2), 247-253. https://doi.org/10.1080/019262302753559588

Species Differences in the Distribution of Drug-Metabolizing Enzymes in the Pancreas. / Ulrich, Alexis B.; Standop, Jens; Schmied, Bruno M.; Schneider, Matthias B.; Lawson, Terence A.; Pour, Parviz M.

In: Toxicologic Pathology, Vol. 30, No. 2, 02.2002, p. 247-253.

Research output: Contribution to journalArticle

Ulrich, AB, Standop, J, Schmied, BM, Schneider, MB, Lawson, TA & Pour, PM 2002, 'Species Differences in the Distribution of Drug-Metabolizing Enzymes in the Pancreas', Toxicologic Pathology, vol. 30, no. 2, pp. 247-253. https://doi.org/10.1080/019262302753559588
Ulrich, Alexis B. ; Standop, Jens ; Schmied, Bruno M. ; Schneider, Matthias B. ; Lawson, Terence A. ; Pour, Parviz M. / Species Differences in the Distribution of Drug-Metabolizing Enzymes in the Pancreas. In: Toxicologic Pathology. 2002 ; Vol. 30, No. 2. pp. 247-253.
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