PT  - JOURNAL ARTICLE
AU  - IKEDA, MASAYUKI
AU  - TANAKA, SHIRO
AU  - KATAYAMA, TOMOKO
TI  - Inhibitory Effect of 2-Diethylaminoethyl 2,2-Diphenylvalerate Hydrochloride (SKF 525-A) on Aromatic Hydroxylation and Phenolic Glucuronidation
DP  - 1968 Jan 01
TA  - Molecular Pharmacology
PG  - 38--43
VI  - 4
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/4/1/38.short
4100  - http://molpharm.aspetjournals.org/content/4/1/38.full
SO  - Mol Pharmacol1968 Jan 01; 4
AB  - Kinetics of the inhibition of two microsomal enzymes of guinea pig liver by SKF 525-A was studied; namely, aryl 4-hydroxylase toward aniline and UDP-glucuronyl transferase toward phenolic glucuronidation of o-aminophenol. In vitro conversion from aniline to p-aminophenol by aryl 4-hydroxylase was noncompetitively inhibited with Ki of 1.7 x 10-4 M, while apparent Km of the reaction was 1.8 x 10-3 M. Excretion of phenol or p-aminophenol in the urine of rats and guinea pigs treated with benzene or aniline, respectively, was markedly decreased by the simultaneous injection of SKF 525-A, indicating the inhibitor was effective in vivo as well as in vitro. Formation of o-aminophenyl glucuronide by UDP-glucuronyl transferase in vitro had apparent Km of 7.1 x 10-5 M, and was inhibited by SKF 525-A also in a noncompetitive manner with Ki of 3.6 x 10-4 M. The in vivo effect of the inhibitor on phenolic glucuronidation was demonstrated with rats and guinea pigs. ACKNOWLEDGMENTS SKF 525-A was a gift from Smith, Kline and French Laboratories, Philadelphia, Pennsylvania. This work was supported in part by a grant from the Fujiwara Memorial Fund.