Skip to main content
Log in

Effects of barbiturates on ultrastructure and polymerization of microtubules in vitro

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Summary

Barbiturates were examined for in vitro effects on ultrastructure of the frog sciatic system and polymerization of microtubules (MT) in a brain supernatant. Exposure for 5–17 h to 2.0 mM barbiturates caused a considerable loss of MT in ganglionic cell bodies and sciatic axons. This was mostly followed by a proliferation of 10 nm filaments. Under similar conditions treatment with 1 mM NaCN or 0.1 mM 2,4-DNP did not change the number or ultrastructure of MT and filaments.

Eight barbiturates, varying in binding ratios to serum albumin and partition coefficients, were tested for effects on polymerization of MT using viscometry. Inhibitory effects were found which correlated with their reported ability to bind to albumin and brain fractions. Dimethylsulphoxide and ethanol were used as solvents for some of the barbiturates. These solvents at 1% had stabilizing effects on MT.

The present results are discussed in relation to previous findings of inhibition of rapid axonal transport in vitro in the frog sciatic system by barbiturates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bamburg, J. R., Shooter, E. M., Wilson, L.: Developmental changes in microtubule protein of chick brain. Biochemistry 12, 1476–1482 (1973)

    Google Scholar 

  • Borisy, G. G.: A rapid method for quantitative determination of microtubule protein using DEAE-cellulose filters. Analyt. Biochem. 50, 373–385 (1972)

    Google Scholar 

  • Borisy, G. G., Olmsted, J. B., Marcum, J. M., Allen, C.: Microtubule assembly in vitro. Fed. Proc. 33, 167–174 (1974)

    Google Scholar 

  • Bush, M. L.: Sedatives and hypnotics. Absorption, fate and excretion. In: Physiological pharmacology, vol. 1, p. 185–218 (Root, W. S. and Hofmann, F. G., eds.). New York-London: Academic Press 1963

    Google Scholar 

  • Byers, M. R.: Structural correlates of rapid axonal transport: Evidence that microtubules may not be directly involved. Brain Res. 75, 97–113 (1974)

    Google Scholar 

  • Edström, A., Hanson, M.: Retrograde axonal transport of proteins in vitro in frog sciatic nerves. Brain Res. 61, 311–320 (1973)

    Google Scholar 

  • Edström, A., Hansson, H.-A., Norström, A.: Inhibition of axonal transport in vitro in frog sciatic nerves by chlorpromazine and lidocaine. Z. Zellforsch. 143, 53–69 (1973)

    Google Scholar 

  • Edström, A., Larsson, H.: Effects of barbiturates on synthesis and rapid axonal transport of protein in vitro in the sciatic system of the frog. Acta physiol. scand. 91, 433–440 (1974)

    Google Scholar 

  • Filner, P., Behnke, O.: Stabilization and isolation of brain microtubules with glycerol and dimethylsulphoxide (DMSO). J. Cell Biol. 59, 99a (1973)

  • Goldbaum, L. R., Smith, P. K.: The interaction of barbiturates with serum albumin and its possible relation to their disposition and pharmacological actions. J. Pharmacol. exp. Ther. 3, 197–209 (1954)

    Google Scholar 

  • Hansson, H.-A., Sjöstrand, J.: Ultrastructural effects of colchicine on the hypoglossal and dorsal vagal neurons of the rabbit. Brain Res. 35, 379–396 (1971)

    Google Scholar 

  • Inoué, S., Borisy, G. G., Kiehart, D. P.: Growth and lability of Chaetopterus oocyte mitotic spindles isolated in the presence of porcine brain tubulin. J. Cell Biol. 62, 175–184 (1974)

    Google Scholar 

  • Karlsson, J.-O., Hansson, H.-A., Sjöstrand, J.: Effects of colchicine on axonal transport and morphology of retinal ganglion cells. Z. Zellforsch. 115, 265–283 (1971)

    Google Scholar 

  • Karnovsky, N. J.: A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J. Cell Biol. 27, 137A (1965)

  • Larsson, H., Edström, A., Hansson, H.-A.: Effects of barbiturates in vitro on protein synthesis, rapid axonal transport and ultrastructure in the frog sciatic system. Acta physiol. scand. 91, 41A-42A (1974)

    Google Scholar 

  • Lee, Y. C., Samson, F. E., Jr., Houston, L. L., Himes, R. H.: The in vitro polymerization of tubulin from beef brain. J. Neurobiol. 5, 317–330 (1974)

    Google Scholar 

  • Liwnicz, B. H., Kristensson, K., Wiśniewsky, H. M., Shelanski, M. L., Terry, R. D.: Observations on axoplasmic transport in rabbits with aluminium-induced neurofibrillary tangles. Brain Res. 80, 413–420 (1974)

    Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurements with folin phenol reagent. J. Cell Biol. 193, 265–275 (1951)

    Google Scholar 

  • Nilsson, L., Siesjö, B. K.: Influence of anaesthetics on the balance between production and utilization of energy in the brain. J. Neurochem. 23, 29–36 (1974)

    Google Scholar 

  • Ochs, S.: Fast transport of materials in mammalian nerve fibers. Science 176, 252–260 (1972)

    Google Scholar 

  • Olmsted, J. B., Borisy, G. G.: Characterization of microtubule assembly in porcine brain extracts by viscometry. Biochemistry 12, 4282–4289 (1973)

    Google Scholar 

  • Olmsted, J. B., Marcum, J. M., Johnson, K. A., Allen, C., Borisy, G. G.: Microtubule assembly: Some possible regulatory mechanisms. J. Supramol. Struct. 2, 429–450 (1974)

    Google Scholar 

  • Quastel, J. H.: Effects of anaesthetics, depressants and tranquilizers on cerebral metabolism. In: Metabolic inhibitors. A comprehensive treatise, vol. II, p. 517–538 (Hochster, R. M. and Quastel, J. H., eds.). New York-London: Academic Press 1963

    Google Scholar 

  • Ueda, I., Kamaya, H.: Kinetic and thermodynamic aspects of the mechanism of general anaesthesia in a model system of firefly luminescence in vitro. Anaesthesiology 38, 425–436 (1973)

    Google Scholar 

  • Weisenberg, R. C.: Microtubule formation in vitro in solutions containing low calcium concentrations. Science 177, 1104–1105 (1972)

    Google Scholar 

  • Wuerker, R. B., Kirkpatrick, J. B.: Neuronal microtubules, neurofilaments and microfilaments. Int. Rev. Cytol. 33, 45–75 (1972)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The present work was supported by grants from Statens Naturvetenskapliga Forskningsråd (No. 2535-0011), Statens Medicinska Forskningsråd (B 75-12x-2543-07), Wilhelm och Martina Lundgrens Vetenskapsfond, Magnus Bergwalls Stifteise och Göteborgs Kungl. Vetenskapsoch Vitterhetssamhälle. Thanks are due to Miss Monica Lindhé for her expert technical assistance.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Edström, A., Hansson, H.A., Larsson, H. et al. Effects of barbiturates on ultrastructure and polymerization of microtubules in vitro . Cell Tissue Res. 162, 35–47 (1975). https://doi.org/10.1007/BF00223260

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00223260

Key words

Navigation