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Journal of Pharmacology And Experimental Therapeutics, Vol. 183, Issue 1, 206-217, 1972
Copyright © 1972 by American Society for Pharmacology and Experimental Therapeutics

A COMPARATIVE STUDY OF THE HEPATIC AND PULMONARY MICROSOMAL MIXED-FUNCTION OXIDASE SYSTEMS IN THE RABBIT

JOHN R. BEND 1, GARY E. R. HOOK 2, ROBERT E. EASTERLING 1, THEODORE F. GRAM 1, and JAMES R. FOUTS 1

1 Pharmacology and Toxicology Branch, National Institute of Environmental health Sciences, National Institutes of Health, Research Triangle Park, North Carolina
2 Pharmacology and Toxicology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina

Rabbit lung microsomal aniline hydroxylase, biphenyl hydroxylase and (+)-benzphetamine demethylase required reduced nicotinamide adenine dinucleotide phosphate and oxygen for maximum activity. In general, the protein-activity, time-activity, substrate concentration-activity and pH-activity curves of aniline hydroxylase, biphenyl hydroxylase and benzphetamine demethylase were similar in microsomes from lung and liver. Cytochrome c, SKF 525A and CO inhibit microsomal mixed-function oxidase in lung as well as in liver. The apparent Km values for biphenyl hydroxylation and (+)-benzphetamine demethylation in lung were not significantly different than those found in liver. However, the apparent Vmax of both activities was slightly, but significantly, higher in lung microsomes (per milligram of microsomal protein). The addition of (+)-benzphetamine to lung microsomes resulted in a typical type I difference spectrum (peak and trough near 385 and 423 nm, respectively) whereas aniline often produced a weak atypical type II difference spectrum in lung (peak near 430 nm with a long trough about 390-415 nm frequently showing a minimum at 410 nm). The apparent K8 for (+)-benzphetamine binding to lung microsomes (0.033 mM) was very similar to that found with liver microsomes (0.036 mM). N-methyl-p-chloroaniline and (+)-benzphetamine demethylase activities were significantly higher in lung microsomes (pen milligram of microsomal protein) than in liver microsomes, although the reverse was true when aminopyrine was used as substrate. Ethylmorphine demethylase activities were not significantly different in microsomes prepared from the two organs.

Submitted on February 28, 1972
Accepted on May 24, 1972




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Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics.