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. 1975 May;7(5):530–537. doi: 10.1128/aac.7.5.530

Inhibition by Levorphanol and Related Drugs of Amino Acid Transport by Isolated Membrane Vesicles from Escherichia coli

Mary J C Holland 1, Eric J Simon 1
PMCID: PMC429177  PMID: 1096802

Abstract

Levorphanol inhibits the transport of the amino acids proline and lysine by cytoplasmic membrane vesicles derived from Escherichia coli. The degree of inhibition increases with increasing levorphanol concentration and ranges from 26% at 10−6 M levorphanol to 92% at 10−3 M levorphanol. The effect is independent of the energy source, since levorphanol inhibits proline uptake to the same extent in the presence of 20 mM d-lactate or 20 mM succinate and in the absence of an exogenous energy source. Levorphanol does not irreversibly alter the ability of membrane vesicles to transport proline, since incubation of membrane vesicles for 15 min in the presence of 0.25 mM levorphanol, a concentration which inhibits proline transport by more than 75%, has no effect on the rate of proline transport by these vesicles once the drug is removed. Both the maximum velocity and the Km of proline transport are modified by levorphanol, hence, the type of inhibition produced by levorphanol is mixed. The inhibitor constant (Ki) for levorphanol inhibition of proline transport is approximately 3 × 10−4 M. Membrane vesicles incubated in the presence of levorphanol accumulate much less proline at the steady state than do control vesicles. Furthermore, the addition of levorphanol to membrane vesicles preloaded to the steady state with proline produces a marked net efflux of proline. Levorphanol does not block either temperature-induced efflux or exchange of external proline with [14C]proline present in the intravesicular pool. Dextrorphan, the enantiomorph of levorphanol, and levallorphan, the N-allyl analogue of levorphanol, inhibit proline and lysine transport in a similar manner. Possible mechanisms of the effects of these drugs on cell membranes are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnes E. M., Jr, Kaback H. R. Beta-galactoside transport in bacterial membrane preparations: energy coupling via membrane-bounded D-lactic dehydrogenase. Proc Natl Acad Sci U S A. 1970 Aug;66(4):1190–1198. doi: 10.1073/pnas.66.4.1190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DAVIS B. D., MINGIOLI E. S. Mutants of Escherichia coli requiring methionine or vitamin B12. J Bacteriol. 1950 Jul;60(1):17–28. doi: 10.1128/jb.60.1.17-28.1950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Devynck M. A., Boquet P. L., Fromageot P. On the mode of action of levallorphan on Escherichia coli: effects on cellular magnesium. Mol Pharmacol. 1971 Nov;7(6):605–610. [PubMed] [Google Scholar]
  4. Gale E. F. Effect of morphine derivatives on lipid metabolism in Staphylococcus aureus. Mol Pharmacol. 1970 Mar;6(2):134–145. [PubMed] [Google Scholar]
  5. Gale E. F. Effects of diacetylmorphine and related morphinans on some biochemical activities of Staphylococcus aureus. Mol Pharmacol. 1970 Mar;6(2):128–133. [PubMed] [Google Scholar]
  6. Greene R., Magasanik B. The mode of action of levallorphan as an inhibitor of cell growth. Mol Pharmacol. 1967 Sep;3(5):453–472. [PubMed] [Google Scholar]
  7. Hirata H., Asano A., Brodie A. F. Respiration dependent transport of proline by electron transport particles from mycobacterium phlei. Biochem Biophys Res Commun. 1971 Jul 16;44(2):368–374. doi: 10.1016/0006-291x(71)90609-7. [DOI] [PubMed] [Google Scholar]
  8. Kaback H. R., Barnes E. M., Jr Mechanisms of active transport in isolated membrane vesicles. II. The mechanism of energy coupling between D-lactic dehydrogenase and beta-galactoside transport in membrane preparations from Escherichia coli. J Biol Chem. 1971 Sep 10;246(17):5523–5531. [PubMed] [Google Scholar]
  9. Kaback H. R., Milner L. S. Relationship of a membrane-bound D-(-)-lactic dehydrogenase to amino acid transport in isolated bacterial membrane preparations. Proc Natl Acad Sci U S A. 1970 Jul;66(3):1008–1015. doi: 10.1073/pnas.66.3.1008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kaback H. R. Transport across isolated bacterial cytoplasmic membranes. Biochim Biophys Acta. 1972 Aug 4;265(3):367–416. doi: 10.1016/0304-4157(72)90014-7. [DOI] [PubMed] [Google Scholar]
  11. Knape H., Boquet P. L., Röschenthaler R. Inhibition of amino acid transport in Escherichia coli cells and its cell membranes. FEBS Lett. 1972 Jan 1;19(4):311–314. doi: 10.1016/0014-5793(72)80068-1. [DOI] [PubMed] [Google Scholar]
  12. Lombardi F. J., Kaback H. R. Mechanisms of active transport in isolated bacterial membrane vesicles. 8. The transport of amino acids by membranes prepared from Escherichia coli. J Biol Chem. 1972 Dec 25;247(24):7844–7857. [PubMed] [Google Scholar]
  13. SIMON E. J. INHIBITION OF BACTERIAL GROWTH BY DRUGS OF THE MORPHINE SERIES. Science. 1964 May 1;144(3618):543–544. doi: 10.1126/science.144.3618.543. [DOI] [PubMed] [Google Scholar]
  14. SIMON E. J., VANPRAAG D. INHIBITION OF RNA SYNTHESIS IN ESCHERICHIA COLI BY LEVORPHANOL. Proc Natl Acad Sci U S A. 1964 May;51:877–883. doi: 10.1073/pnas.51.5.877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. SIMON E. J., VANPRAAG D. SELECTIVE INHIBITION OF SYNTHESIS OF RIBOSOMAL RNA IN ESCHERICHIA COLI BY LEVORPHANOL. Proc Natl Acad Sci U S A. 1964 Jun;51:1151–1158. doi: 10.1073/pnas.51.6.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Short S. A., White D. C., Kaback H. R. Active transport in isolated bacterial membrane vesicles. V. The transport of amino acids by membrane vesicles prepared from Staphylococcus aureus. J Biol Chem. 1972 Jan 10;247(1):298–304. [PubMed] [Google Scholar]
  17. Simon E. J., Garwes D. J., Rand J. Reversible inhibition of RNA phage replication and macromolecular synthesis by levorphanol. Biochem Biophys Res Commun. 1970 Sep 10;40(5):1134–1141. doi: 10.1016/0006-291x(70)90912-5. [DOI] [PubMed] [Google Scholar]
  18. Simon E. J., Schapira L., Wurster N. Effect of levorphanol on putrescine transport in Escherichia coli. Mol Pharmacol. 1970 Nov;6(6):577–587. [PubMed] [Google Scholar]
  19. Simon E. J., Van Praag D., Aronson F. L. The selective inhibition of ribosomal RNA synthesis in E. coli by 2,4-Dinitrophenol. Mol Pharmacol. 1966 Jan;2(1):43–49. [PubMed] [Google Scholar]
  20. Weissbach H., Thomas E., Kaback H. R. Studies on the metabolism of ATP by isolated bacterial membranes: formation and metabolism of membrane-bound phosphatidic acid. Arch Biochem Biophys. 1971 Nov;147(1):249–254. doi: 10.1016/0003-9861(71)90332-8. [DOI] [PubMed] [Google Scholar]
  21. Wurster N., Elsbach P., Rand J., Simon E. J. Effects of levorphanol on phospholipid metabolism and composition in Escherichia coli. Biochim Biophys Acta. 1971 Nov 5;248(2):282–292. doi: 10.1016/0005-2760(71)90016-6. [DOI] [PubMed] [Google Scholar]

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