Skip to main content
Log in

Effects of salsolinol on cultivated endothelial cells

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

In view of neurotoxic properties of tetrahydroisoquinolines (TIQ's) there are open questions also in regard to the disturbance of the blood-brain barrier. Because endothelial cells are an important element of this barrier the present study was designed to assess the influence of salsolinol (a TIQ formed by condensation of dopamine and acetaldehyde) on cultivated endothelial cells by physiological, biochemical and morphological investigations. For the investigations we used aortic endothelial cells because of a variety of similarities in physiology and biochemistry to brain capillary endothelial cells. Cytotoxic effects estimated by cell counting after 72 h treatment with salsolinol (IC50=38 μmol/l) were possibly caused by mitochondrial damages. Already after 2 h severe ultrastructural alterations of many mitochondria could be observed. The respiration activity of the cells was always inhibited after treatment with salsolinol for some hours. The damage of the mitochondria by salsolinol was not connected with inhibition of the activity of succinate dehydrogenase and cytochrome c+c1. Nevertheless the damages of mitochondrial integrity support the hypothesis that the neurotoxic effect of salsolinol is primarily caused by damaging the endothelial cells associated with a disturbance of blood-brain barrier.

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

  1. Ohta, S., Tachikawa, O., Makino, Y., Tasaki, Y., and Hirobe, M. 1990. Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ), a possible Parkinsonism inducing substance, in an animal model of a poor Debrisoquine metabolizer. Life Sci. 46:599–605.

    Google Scholar 

  2. Nagatsu, T., and Yoshida, M. 1988. An endogenous substance of the brain, tetrahydroisoquinoline, produces Parkinsonism in primates with decreased dopamine, tyrosine hydroxylase and biopterin in the nigrostriatal regions. Neurosci. Lett. 87:178–182.

    Google Scholar 

  3. Ohta, S., M. Makino, Y., Tachikawa, O., and Hirobe, M. 1987. Tetrahydroisoquinoline and 1-methyl-tetrahydroisoquinoline are present in the human brain: relation to Parkinson's disease. Biomed. Res. 8:453–456.

    Google Scholar 

  4. Dostert, P., Strolin Benedetti, M., and Dordain, G. 1988. Dopamine-derived alkaloids in alcoholism and in Parkinson's and Huntington's diseases. J. Neural. Transm. 74:61–74.

    Google Scholar 

  5. Dostert, P., Strolin Benedetti, M., and Dedieu, M. 1987. Ratio of enantiomers of salsolinol in human urine. Pharmacol. Toxicol. 60 [Suppl.] 1:13.

    Google Scholar 

  6. Suzuki, K., Mizuno, Y., and Yoshida, M. 1990. Inhibition of mitochondrial respiration by 1,2,3,4-tetrahydroisoquinoline-like endogenous alkaloids in mouse brain. Neurochem. Res. 15:705–710.

    Google Scholar 

  7. Melzig, M., and Möller, U. 1991. Effect of trypsin and zymosan on the respiration of cultivated endothelial cells. Pharmazie 46:46–48.

    Google Scholar 

  8. Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65:55–63.

    Google Scholar 

  9. Melzig, M., and Dienwiebel, U. 1990. Is the estimation of the activity of MTT-reduction suitable for the determination of the basal cytotoxicity? Pharmazie 45:515–517.

    Google Scholar 

  10. Suzuki, K., Mizuno, Y., and Yoshida, M. 1988. Inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity and ATP synthesis by tetrahydroisoquinoline. Neurosci. Lett. 86:105–108.

    Google Scholar 

  11. Booth, R. G., Castagnoli, N., and Rollema, H. 1989. Intracerebral microdialysis neurotoxicity studies of quinoline and isoquinoline derivatives related to MPTP/MPP+. Neurosci. Lett. 100:306–312.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Melzig, M.F., Zipper, J. Effects of salsolinol on cultivated endothelial cells. Neurochem Res 18, 689–693 (1993). https://doi.org/10.1007/BF00966783

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00966783

Key Words

Navigation