The effect of substrates and inhibitors of cytochrome P-450 on the NADPH inhibition of the ATP-dependent, hepatic, microsomal calcium pump.
In hepatic microsomes one or more isozymes of cytochrome P-450 inhibits the ATP-dependent Ca2+ pump. This inhibition is reversible by GSH and appears to be due to a direct oxidation of the pump proteins by the oxygenated cytochrome. To determine which isozyme mediates this inhibition, we have examined the effect of various substrates and inhibitors on the NADPH inhibition of Ca2+ uptake. We find that aminopyrine, benzphetamine and SKF-525A reverse this inhibition while a number of other substrates do not. This pattern suggests that a previously unreported isozyme of cytochrome P-450 mediates the Ca2+ pump inhibition.
Srivastava
S P
SP
Department of Pharmacology, University of Minnesota, Minneapolis 55455.
Chen
N Q
NQ
Holtzman
J L
JL
D000632:Aminopyrine / Q000494:pharmacology; D000818:Animals; D001589:Benzphetamine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D000632:Aminopyrine; D001589:Benzphetamine; D009249:NADP; C029899:imidazole; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D000252:Calcium-Transporting ATPases; D002118:Calcium; D008797:Metyrapone