Molecular Pharmacology, Vol 6, 577-587, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Effect of Levorphanol on Putrescine Transport in Escherichia coli

¹ Department of Medicine, New York University Medical Center, New York, New York 10016

The disappearance of cellular putrescine observed when Escherichia coli cultures were treated with levorphanol was shown to be largely the result of an acceleration of putrescine efflux produced by the drug. The efflux of putrescine from E. coli exhibited a stringent requirement for metabolic energy. It was found to be greatly reduced by carbon source starvation, by treatment with metabolic inhibitors, or by low temperature. The efflux of putrescine stimulated by levorphanol was also virtually abolished by such treatments. Levorphanol also inhibited the uptake of putrescine by E. coli cells. Evidence is presented which indicates that the inhibition of uptake and the stimulation of efflux represent separate effects of levorphanol. Competition between levorphanol and putrescine for a carrier or binding site was ruled out by kinetic experiments, which showed that inhibition of putrescine uptake by levorphanol was not competitive. The effect of levorphanol on the putrescine pool was readily reversible. Replenishment began without measurable delay upon removal of the drug. Levorphanol also produced reversible alterations in the permeability of E. coli to most, if not all, amino acids, spermidine, and K⁺. Possible mechanisms of the effects of levorphanol on cell membranes are discussed.

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ACKNOWLEDGMENTS The authors wish to express their sincere thanks to Dr. Federico Welsch, Department of Biochemistry, Dartmouth Medical College, for performing the ATP determinations. They also gratefully acknowledge the helpful discussions and critical reading of this manuscript by Dr. Peter Elsbach.