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Molecular Pharmacology, Vol 7, 697-705, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

The Metabolism of Aminopyrine in Chick Embryo Hepatic Cell Culture: Effects of Competitive Substrates and Carbon Monoxide

ALAN POLAND 1 and ATTALLAH KAPPAS 1

1 The Rockefeller University, New York, New York 10021

Chick embryonic liver cells grown in monolayer cultures metabolize aminopyrine to 4-aminoantipyrine, which is released into the medium. This N-demethylation is performed by liver cell cultures but not by renal or intestinal cell cultures from chick embryos. The formation of 4-aminoantipyrine is linear with time and is inhibited by SKF 525-A (2-diethylaminoethyl 2,2-diphenylvalerate HCl), piperonyl butoxide, hexobarbital, lauric acid, and testosterone. Inhibition in all cases is at least partially reversible. The rate of 4-aminoantipyrine formation is also reversibly inhibited by carbon monoxide. From the CO:O2 ratio and rate of formation of the metabolite, it is possible to estimate the partition coefficient, KL, for cytochrome P-450 in living cells, which agrees quite well with estimates from incubations in vitro.

Note:
ACKNOWLEDGMENT We would like to thank Mrs. Sandra Weinstein for excellent technical assistance.

Submitted on April 23, 1971







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