Pulmonary accumulation of drugs in vitamin a deficiency

The effect of vitamin A deficiency on the uptake of several drug substrates in rat lung slices was determined. Vitamin A deficiency resulted in significant increases in the pulmonary accumulation of imipramine, chlorpromazine, 5-hydroxytryptamine and norepinephrine. The enhanced uptake of 5-hydroxytryptamine by deficient slices was probably due to a decrease in pulmonary monoamine oxidase (MAO) activity, since accumulation of this amine was similar in control and deficient slices that had been preincubated in pargyline, an inhibitor of MAO. In contrast, pulmonary uptake of methadone and paraquat was not affected in vitamin A deficiency. These results suggest that the enhanced susceptibility of the respiratory tract of vitamin A deficient animals to toxic chemicals may be due in part to an increase in the accumulation of the chemicals by the lung.