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. 1976 Feb 1;68(2):395–402. doi: 10.1083/jcb.68.2.395

Effects of local anesthetics on cell morphology and membrane-associated cytoskeletal organization in BALB/3T3 cells

PMCID: PMC2109628  PMID: 1245553

Abstract

Tertiary amine local anesthetics (dibucaine, tetracaine, procaine) reversibly affect the morphology of untransformed BALB/3T3 cells and the organization of membrane-associated cytoskeletal elements. In the presence of these drugs cells contract and become rounded in shape with the appearance of numerous surface "blebs." Electron microscope examination of anesthetic-treated cells revealed significant reductions in plasma membrane-associated microtubules and microfilaments and/or their plasma membrane attachment. The relationship of the findings on local anesthetic-induced changes in cellular cytoskeletal systems is discussed in relation to previous proposals on plasma membrane organization and control of cell surface receptor topography and mobility.

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Selected References

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  1. Allison A. C., Nunn J. F. Effects of general anaesthetics on microtubules: a possible mechanism of anaesthesia. Lancet. 1968 Dec 21;2(7582):1326–1329. doi: 10.1016/s0140-6736(68)91821-7. [DOI] [PubMed] [Google Scholar]
  2. Blaustein M. P., Goldman D. E. Action of anionic and cationic nerve-blocking agents: experiment and interpretation. Science. 1966 Jul 22;153(3734):429–432. doi: 10.1126/science.153.3734.429. [DOI] [PubMed] [Google Scholar]
  3. Carter S. B. Cell movement and cell spreading: a passive or an active process? Nature. 1970 Feb 28;225(5235):858–859. doi: 10.1038/225858a0. [DOI] [PubMed] [Google Scholar]
  4. Chen S. S. Studies of radiocalcium efflux in single barnacle muscle fibres: effects of procaine and external divalent cations. J Physiol. 1974 Apr;238(2):313–328. doi: 10.1113/jphysiol.1974.sp010526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eyring H., Woodbury J. W., D'Arrigo J. S. A molecular mechanism of general anesthesia. Anesthesiology. 1973 May;38(5):415–424. doi: 10.1097/00000542-197305000-00001. [DOI] [PubMed] [Google Scholar]
  6. FEINSTEIN M. B. REACTION OF LOCAL ANESTHETICS WITH PHOSPHOLIPIDS. A POSSIBLE CHEMICAL BASIS FOR ANESTHESIA. J Gen Physiol. 1964 Nov;48:357–374. doi: 10.1085/jgp.48.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fink B. R., Byers M. R., Middaugh M. E. Dynamics of colchicine effects on rapid axonal transport and axonal morphology. Brain Res. 1973 Jun 29;56:299–311. doi: 10.1016/0006-8993(73)90343-0. [DOI] [PubMed] [Google Scholar]
  8. Gail M. H., Boone C. W. Procaine inhibition of fibroblast motility and proliferation. Exp Cell Res. 1972 Jul;73(1):252–255. doi: 10.1016/0014-4827(72)90130-9. [DOI] [PubMed] [Google Scholar]
  9. Giotta G. J., Chan D. S., Wang H. H. Binding of spin-labeled local anesthetics to phosphatidylcholine and phosphatidylserine liposomes. Arch Biochem Biophys. 1974 Aug;163(2):453–458. doi: 10.1016/0003-9861(74)90501-3. [DOI] [PubMed] [Google Scholar]
  10. Godman G. C., Miranda A. F., Deitch A. D., Tanenbaum S. W. Action of cytochalasin D on cells of established lines. III. Zeiosis and movements at the cell surface. J Cell Biol. 1975 Mar;64(3):644–667. doi: 10.1083/jcb.64.3.644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hansch C., Anderson S. M. The structure-activity relationship in barbiturates and its similarity to that in other narcotics. J Med Chem. 1967 Sep;10(5):745–753. doi: 10.1021/jm00317a001. [DOI] [PubMed] [Google Scholar]
  12. Haschke R. H., Byers M. R., Fink B. R. Effects of lidocaine on rabbit brain microtubular protein. J Neurochem. 1974 May;22(5):837–843. doi: 10.1111/j.1471-4159.1974.tb04302.x. [DOI] [PubMed] [Google Scholar]
  13. Hauser H., Penkett S. A., Chapman D. Nuclear magnetic resonance spectroscopic studies of procaine hydrochloride and tetracaine hydrochloride at lipid-water interfaces. Biochim Biophys Acta. 1969;183(3):466–475. doi: 10.1016/0005-2736(69)90161-8. [DOI] [PubMed] [Google Scholar]
  14. Hinkley R. E., Telser A. G. The effects of halothane on cultured mouse neuroblastoma cells. I. Inhibition of morphological differentiation. J Cell Biol. 1974 Nov;63(2 Pt 1):531–540. doi: 10.1083/jcb.63.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hubbell W. L., Metcalfe J. C., Metcalfe S. M., McConnell H. M. The interaction of small molecules with spin-labelled erythrocyte membranes. Biochim Biophys Acta. 1970 Dec 1;219(2):415–427. doi: 10.1016/0005-2736(70)90219-1. [DOI] [PubMed] [Google Scholar]
  16. Juliano R. L., Kimelberg H. K., Papahadjopoulos D. Synergistic effects of a membrane protein (spectrin) and Ca 2+ on the Na + permeability of phospholipid vesicles. Biochim Biophys Acta. 1971 Sep 14;241(3):894–905. doi: 10.1016/0005-2736(71)90017-4. [DOI] [PubMed] [Google Scholar]
  17. Kirschner M. W., Williams R. C. The mechanism of microtubule assembly in vitro. J Supramol Struct. 1974;2(2-4):412–428. doi: 10.1002/jss.400020229. [DOI] [PubMed] [Google Scholar]
  18. Lever M. J., Miller K. W., Paton W. D., Smith E. B. Pressure reversal of anaesthesia. Nature. 1971 Jun 11;231(5302):368–371. doi: 10.1038/231368a0. [DOI] [PubMed] [Google Scholar]
  19. Marchesi V. T., Steers E., Jr Selective solubilization of a protein component of the red cell membrane. Science. 1968 Jan 12;159(3811):203–204. doi: 10.1126/science.159.3811.203. [DOI] [PubMed] [Google Scholar]
  20. Maslow D. E., Mayhew E. Histotypic cell aggregation in the presence of cytochalasin B. J Cell Sci. 1974 Dec;16(3):651–663. doi: 10.1242/jcs.16.3.651. [DOI] [PubMed] [Google Scholar]
  21. Merin R. G., Kumazawa T., Honig C. R. Reversible interaction between halothane and Ca++ on cardiac actomyosin adenosine triphosphatase: mechanism and significance. J Pharmacol Exp Ther. 1974 Jul;190(1):1–14. [PubMed] [Google Scholar]
  22. Nicolson G. L. Concanavalin A as a quantitative and ultrastructural probe for normal and neoplastic cell surfaces. Adv Exp Med Biol. 1975;55:153–172. doi: 10.1007/978-1-4684-0949-9_8. [DOI] [PubMed] [Google Scholar]
  23. Nicolson G. L. The interactions of lectins with animal cell surfaces. Int Rev Cytol. 1974;39:89–190. doi: 10.1016/s0074-7696(08)60939-0. [DOI] [PubMed] [Google Scholar]
  24. O'brien J. R. Platelet aggregation: Part I Some effects of the adenosine phosphates, thrombin, and cocaine upon platelet adhesiveness. J Clin Pathol. 1962 Sep;15(5):446–452. doi: 10.1136/jcp.15.5.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Olmsted J. B., Marcum J. M., Johnson K. A., Allen C., Borisy G. G. Microtuble assembly: some possible regulatory mechanisms. J Supramol Struct. 1974;2(2-4):429–450. doi: 10.1002/jss.400020230. [DOI] [PubMed] [Google Scholar]
  26. Papahadjopoulos D., Jacobson K., Poste G., Shepherd G. Effects of local anesthetics on membrane properties. I. Changes in the fluidity of phospholipid bilayers. Biochim Biophys Acta. 1975 Jul 18;394(4):504–519. doi: 10.1016/0005-2736(75)90137-6. [DOI] [PubMed] [Google Scholar]
  27. Papahadjopoulos D. Studies on the mechanism of action of local anesthetics with phospholipid model membranes. Biochim Biophys Acta. 1972 Apr 18;265(2):169–186. doi: 10.1016/0304-4157(72)90001-9. [DOI] [PubMed] [Google Scholar]
  28. Poste G., Allison A. C. Membrane fusion. Biochim Biophys Acta. 1973 Dec 28;300(4):421–465. doi: 10.1016/0304-4157(73)90015-4. [DOI] [PubMed] [Google Scholar]
  29. Poste G., Papahadjopoulos D., Jacobson K., Vail W. J. Effects of local anesthetics on membrane properties. II. Enhancement of the susceptibility of mammalian cells to agglutination by plant lectins. Biochim Biophys Acta. 1975 Jul 18;394(4):520–539. doi: 10.1016/0005-2736(75)90138-8. [DOI] [PubMed] [Google Scholar]
  30. Poste G., Papahadjopoulos D., Jacobson K., Vail W. J. Local anaesthetics increase susceptibility of untransformed cells to agglutination by concanavalin A. Nature. 1975 Feb 13;253(5492):552–554. doi: 10.1038/253552a0. [DOI] [PubMed] [Google Scholar]
  31. Poste G., Reeve P. Agglutination of normal cells by plant lectins following infection with nononcogenic viruses. Nat New Biol. 1972 May 24;237(73):113–114. doi: 10.1038/newbio237113a0. [DOI] [PubMed] [Google Scholar]
  32. Rabinovitch M., DeStefano M. J. Manganese stimulates adhesion and spreading of mouse sarcoma I ascites cells. J Cell Biol. 1973 Oct;59(1):165–176. doi: 10.1083/jcb.59.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rabinovitch M., DeStefano M. Cell to substrate adhesion and spreading: inhibition by cationic anesthetics. J Cell Physiol. 1975 Apr;85(2 Pt 1):189–193. doi: 10.1002/jcp.1040850205. [DOI] [PubMed] [Google Scholar]
  34. Rabinovitch M., Destefano M. J. Macrophage spreading in vitro. III. The effect of metabolic inhibitors, anesthetics and other drugs on spreading induced by subtilisin. Exp Cell Res. 1974 Sep;88(1):153–162. doi: 10.1016/0014-4827(74)90629-6. [DOI] [PubMed] [Google Scholar]
  35. Ritchie J. M., Greengard P. On the mode of action of local anesthetics. Annu Rev Pharmacol. 1966;6:405–430. doi: 10.1146/annurev.pa.06.040166.002201. [DOI] [PubMed] [Google Scholar]
  36. Roth S., Seeman P. All lipid-soluble anaesthetics protect red cells. Nat New Biol. 1971 Jun 30;231(26):284–285. doi: 10.1038/newbio231284a0. [DOI] [PubMed] [Google Scholar]
  37. Ryan G. B., Unanue E. R., Karnovsky M. J. Inhibition of surface capping of macromolecules by local anaesthetics and tranquillisers. Nature. 1974 Jul 5;250(461):56–57. doi: 10.1038/250056a0. [DOI] [PubMed] [Google Scholar]
  38. SKOU J. C. Local anaesthetics. VI. Relation between blocking potency and penetration of a monomolecular layer of lipoids from nerves. Acta Pharmacol Toxicol (Copenh) 1954;10(4):325–337. doi: 10.1111/j.1600-0773.1954.tb01349.x. [DOI] [PubMed] [Google Scholar]
  39. Seeman P. The membrane actions of anesthetics and tranquilizers. Pharmacol Rev. 1972 Dec;24(4):583–655. [PubMed] [Google Scholar]
  40. Sheetz M. P., Singer S. J. Biological membranes as bilayer couples. A molecular mechanism of drug-erythrocyte interactions. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4457–4461. doi: 10.1073/pnas.71.11.4457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Spooner B. S., Yamada K. M., Wessells N. K. Microfilaments and cell locomotion. J Cell Biol. 1971 Jun;49(3):595–613. doi: 10.1083/jcb.49.3.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wilson L., Bryan J., Ruby A., Mazia D. Precipitation of proteins by vinblastine and calcium ions. Proc Natl Acad Sci U S A. 1970 Jul;66(3):807–814. doi: 10.1073/pnas.66.3.807. [DOI] [PMC free article] [PubMed] [Google Scholar]

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