Species differences in the distribution of drug-metabolizing enzymes in the pancreas.
We investigated the cellular expression of 9 cytochrome P450-isozymes (CYP1A1, CYPIA2, CYP2B6, CYP2C8,9,19, CYP2D1, CYP2E1, CYP3A1, CYP3A2, CYP3A4) and 3 glutathione S-transferase-isozymes (GST-pi, GST-alpha. GST-mu) 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-alpha, GST-mu), rat (CYP2C8,9, 19). rabbit (CYP1A2, CYP2B6, GST-pi), and pig (CYP1AI). 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.
Ulrich
Alexis B
AB
UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha 68198-6805, USA.
Standop
Jens
J
Schmied
Bruno M
BM
Schneider
Matthias B
MB
Lawson
Terence A
TA
Pour
Parviz M
PM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002648:Child; D002675:Child, Preschool; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis; D019388:Cytochrome P-450 CYP1A2 / Q000032:analysis; D065702:Cytochrome P-450 CYP2B6; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000032:analysis; D010179:Pancreas / Q000201:enzymology*; D013045:Species Specificity
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; D005982:Glutathione Transferase