Induction of CYP1A1 and CYP2E1 in rat liver by histamine: binding and kinetic studies.
Histamine (HA) may bind to cytochrome P450 (CYP450) in rat liver microsomes. The CYP450-HA complex seems to regulate some cellular processes such as proliferation. In the present work, it is shown that HA increases the activity and protein level of CYP1A1 and CYP2E1, in vivo. CYP1A1 is associated with polycyclic aromatic hydrocarbon-mediated carcinogenesis and CYP2E1 with liver damage by oxidative stress. Studies of enzyme kinetics and binding with rat liver microsomes and supersomes were carried out to determine whether HA is a substrate of CYP1A1 and/or CYP2E1. The lack of NADPH oxidation in the presence of HA showed that it is not a substrate for CYP1A1. Activity measurements using the O-dealkylation of ethoxyresorufin indicated that HA is a mixed-type inhibitor of CYP1A1 in both microsomes and supersomes. On the other hand, HA induced a significant NADPH oxidation catalyzed by CYP2E1 supersomes, strongly suggesting that HA is a substrate for this isoform. Furthermore, HA is consumed in the presence of CYP2E1-induced microsomes and supersomes, as determined by o-phtalaldehyde complexes with HA by HPLC. The present findings may contribute to understand better the physiological function of CYP450 in relation with inflammation and other physiological processes in which HA may have a relevant role.
Dávila-Borja
Víctor M
VM
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, P.O. Box 70228, Mexico, DF 04510, Mexico.
Belmont
Javier A
JA
Espinosa
J Javier
JJ
Moreno-Sánchez
Rafael
R
Albores
Arnulfo
A
Montero
Regina D
RD
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000187:drug effects* / Q000378:metabolism; D003640:Dealkylation; D004790:Enzyme Induction / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010078:Oxazines / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011485:Protein Binding; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D010078:Oxazines; D020033:Protein Isoforms; D009249:NADP; C007649:ethoxyresorufin; D006632:Histamine; D019392:Cytochrome P-450 CYP2E1; D019363:Cytochrome P-450 CYP1A1