Effects of disulfiram and coprine on rat brain tryptophan hydroxylation in vivo
- 24 Downloads
The effects of disulfiram and coprine on brain tryptophan hydroxylation, and on the brain-levels of serotonin and 5-hydroxyindole-3-acetic acid, were studied in 45 and 235 days old rats. Both drugs were found to affect the parameters measured. Disulfiram increased the rate of tryptophan hydroxylation and the serotonin level in young rats, while these parameters appeared to be unaffected in old disulfiram-treated rats. In contrast, coprine increased the rate of tryptophan hydroxylation and possibly also the serotonin level in old rats while no significant effects were seen in young coprine-treated rats. Regarding the 5-hydroxyindole-3-acetic acid concentration, this appeared to be increased by disulfiram in both age-groups, while no significant effects were found with coprine. The lack of similarity in the action of disulfiram and coprine, which are both potent aldehyde dehydrogenase inhibitors, suggests that the effects found were not caused by an impaired metabolism of monoamine-derived biogenic aldehydes.
Key WordsAldehyde dehydrogenase inhibitors coprine disulfiram serotonin tryptophan hydroxylation 5-hydroxyindole-3-acetic acid
Unable to display preview. Download preview PDF.
- 3.Fukumori, R., Minegishi, A., Satoh, T., Kitagawa, H., and Yanaura, S. 1980. Changes in the serotonin and 5-hydroxyindoleacetic acid contents in rat brain after ethanol and disulfiram treatments. Europ. J. Pharmacol. 61:199–202.Google Scholar
- 5.Lindberg, P., Bergman, R., and Wickberg, B. 1974. Isolation and structure of coprine, a novel physiologically active cyclopropane derivative from Coprinus atramentarius and its synthesis via 1-aminocyclopropanol. J. Chem. Soc. Chem. Commun. 1974:946–947.Google Scholar
- 6.Pettersson, H., and Tottmar, O. 1982. Inhibition of aldehyde dehydrogenases in rat brain by disulfiram and coprine. J. Neurochem. 38:628–634.Google Scholar
- 7.Fujisawa, H., Yamauchi, T., Nakata, H., and Okuno, S. 1984. Regulation of tyrosine 3-monooxygenase and tryptophan 5-nonooxygenase by phosphorylation-dephosphorylation. Pages 167–183,in Cohen P. (ed.), Enzyme regulation by reversible phosphorylation-further advances, Amsterdam: Elsevier.Google Scholar
- 8.Hamon, M., Bourgoin, S., Artaud, F., and El Mestikawy, S. 1981. The respective roles of tryptophan uptake and tryptophan hydroxylase in the regulation of serotonin synthesis in the central nervous system. J. Physiol., Paris 77:269–279.Google Scholar
- 12.Curzon, G., and Sarna, G. S. 1984. Tryptophan transport to the brain: newer findings and older ones reconsidered. Pages 145–160,in Schlossberger, G. G., Kochen, W., Linzen, B., and Steinhart, H. (eds.), Progress in tryptophan and serotonin research, Berlin-New York: W. de Gruyter & Co.Google Scholar