Effects of muroctasin on the activities of drug metabolizing enzymes in liver microsomes of rats.
1. Effects of repeated administration of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys (L18), muroctasin) to female rats on the activities of drug metabolizing enzymes in liver microsomes were examined. The in vitro effects of the compound on the activities of drug metabolizing enzymes in liver microsomes from male rats were also investigated. 2. The subcutaneous administration of MDP-Lys (L18) at a dose of 1 mg/kg (high dose) caused slight but significant decrease in the contents of cytochrome P-450 and cytochrome b5. The daily subcutaneous injection at a dose of 0.1 mg/kg (middle dose) resulted in the induction of aminopyrine N-demethylase, aniline hydroxylase and 7-ethoxycoumarin O-deethylase. Such induction of the enzymes was seen only when calculated on the basis of microsomal protein but not wet weight of livers. The changes were relatively small as compared with those caused by phenobarbital. 3. At one week after the last injection of the high dose of MDP-Lys (L18), slightly higher levels of the contents of cytochrome P-450 and cytochrome b5 and the activity of NADPH-cytochrome c reductase were noted. The cessation of the administration tended to increase the activities of drug metabolizing enzymes in rats treated with the high dose of the drug. These changes were seen only when the activities were calculated on the basis of mg of microsomal protein. 4. MDP-Lys (L18) inhibited drug metabolizing enzymes in vitro to various extents depending on the substrate used.(ABSTRACT TRUNCATED AT 250 WORDS)
Kamataki
T
T
Division of Analytical Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Komori
M
M
Iwasaki
M
M
Ohi
H
H
Kitada
M
M
Miura
T
T
Ono
K
K
D015660:7-Alkoxycoumarin O-Dealkylase; D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors; D000815:Aniline Hydroxylase / Q000037:antagonists & inhibitors; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism*; D015786:Cytochromes b5; D004579:Electron Transport; D005260:Female; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000378:metabolism; D009929:Organ Size; D010105:Oxygenases / Q000037:antagonists & inhibitors; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000276:Adjuvants, Immunologic; D003573:Cytochrome b Group; D003580:Cytochromes; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D009245:NADH Dehydrogenase; C036866:romurtide; D010634:Phenobarbital