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J R Fouts

Publications and source records attributed to J R Fouts.

117 records · Page 7Linked to original sources

Postnatal development of mixed-function oxidation as measured in microsomes from the small intestine and liver of rabbits.

The postnatal development of aminopyrine N-demethylase, aniline 4-hydroxylase, benzpyrene hydroxylase, biphenyl 4-hydroxylase, 7-ethoxycoumarin 0-deethylase activities, NADPH-cytochrome c reductase, and cytochrome P-450 was compared in microsomes from the liver and small intestine of New Zealand white rabbits. Apart from hepatic aniline hydroxylase activity, all of the xenobiotic-metabolizing enzyme activities examined had a similar pattern of development in the liver and small intestine. In both tissues the ability to metabolize xenobiotics was generally undetectable at 2 days of age and remained relatively low for the first 20 days of life. Theresfter, a rapid 2- to 5-fold increase in all the enzyme activity studied was noted, and adult values were reached or exceeded by 30 days of age. Subsequent development of xenobiotic-metabolizing enzyme activities in the small intestine, but not in the liver, exhibited a transient fall at 50 days of age before adult activities were attained after 75 days of age. The developmental pattern of cytochrome P-450 in the small intestine closely resembled that of the xenobiotic-metabolizing enzyme activities, but in the liver this correlation was less exact.

Aging↗

7-ethoxycoumarin O-deethylation activity in viable basal and differentiated keratinocytes isolated from the skin of the hairless mouse.

Epidermal cells in suspension were prepared from the skin of hairless mice by digestion of skin strips with pronase. The viability of cells in such suspensions was routinely greater than 75%. Fractions enriched in different cell types were prepared from the original cell suspensions using metrizamide gradients and elutriation techniques. These fractions were studied histologically and enzymically. The cells of greater size both were more differentiated and had higher xenobiotic metabolizing enzyme activities. Also increasing in parallel with cell size were parameters such as protein to DNA ratios. Lowest in all respects were basal cells (size, enzyme activities, protein/DNA ratios, etc.). The present techniques seem superior to previously described methods for isolating skin cells for study of xenobiotic metabolisms and possible distribution of these metabolisms in different cell types.

Animals↗

Biochemical properties of some microsomal xenobiotic-metabolizing enzymes in rabbit small intestine.

Comparison of xenobiotic-metabolizing enzymes in rabbit small intestinal and hepatic microsomal fractions showed mainly quantitative differences; most of the activities were two to seven times higher in liver than in intestine. However, UDP-glucuronyltransferase activity was higher in intestine than in liver. The apparent absence of benzene hydroxylase in small intestine was the only qualitative difference noticed. Aniline hydroxylase, aminopyrine N-demethylase, and aryl hydrocarbon dydroxylase were characterized in intestinal microsomes and compared to those of liver. Distribution of these enzymes along the entire length of small intestine showed that maximum activities of the enzymes were present in the proximal 60 cm of the intestine. All the enzymes in both tissues required NADPH and O2 for maximum activity and were inhibited by cytochrome c, SKF 525-A, and CO. The in vitro addition of drug substrates to microsomal fractions of both tissues produced typical type I and type II binding spectra. Comparison of the relationships between activities and pH, duration of incubation, and substrate and protein concentration suggested that the rabbit intestinal and hepatic xenobiotic-metabolizing enzymes studied have similar characteristics.

Aminopyrine N-Demethylase↗