Abstract
1. Acute administration of ethanol exerts a biphasic effect on the concentrations of rat brain tryptophan, 5-hydroxytryptamine and 5-hydroxyindol-3-ylacetic acid. Both effects are associated with corresponding changes in the availability of circulating free tryptophan. 2. The initial increases in the above concentrations are prevented by ergotamine, are unaltered by allopurinol and are potentiated by theophylline, whereas the later decreases are prevented by both ergotamine and allopurinol. 3. It is suggested that the initial enhancement by ethanol of brain tryptophan metabolism is caused by catecholamine-mediated lipolysis followed by displacement of protein-bound serum tryptophan, whereas the activation of liver tryptophaan pyrrolase, which is produced by the same mechanism, leads to the later decreases in the brain concentrations of tryptophan and its metabolites. 4. The initial effects of ethanol can be reproduced by an equicaloric dose of sucrose, and a comparison of the two treatments alone could therefore be misleading. 5. The effects of ethanol on liver and brain tryptophan metabolism have also been examined in mice, and a comparison of the results with those previously reported suggests that the ethanol effects are strain-dependent.
Full text
PDF









Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Badawy A. A., Evans M. Animal liver tryptophan pyrrolases: Absence of apoenzyme and of hormonal induction mechanism from species sensitive to tryptophan toxicity. Biochem J. 1976 Jul 15;158(1):79–88. doi: 10.1042/bj1580079. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Badawy A. A., Evans M. Letter: Tryptophan plus a pyrrolase inhibitor for depression. Lancet. 1975 Nov 1;2(7940):869–869. doi: 10.1016/s0140-6736(75)90258-5. [DOI] [PubMed] [Google Scholar]
- Badawy A. A., Evans M. The effects of ethanol on tryptophan pyrrolase activity and their comparison with those of phenobarbitone and morphine. Adv Exp Med Biol. 1975;59:229–251. doi: 10.1007/978-1-4757-0632-1_15. [DOI] [PubMed] [Google Scholar]
- Badawy A. A., Evans M. The mechanism of inhibition of rat liver tryptophan pyrrolase activity by 4-hydroxypyrazolo(3,4-d)pyrimidine (Allopurinol). Biochem J. 1973 Jul;133(3):585–591. doi: 10.1042/bj1330585. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Badawy A. A., Evans M. The regulation of rat liver tryptophan pyrrolase activity by reduced nicotinamide-adenine dinucleotide (phosphate). Experiments with glucose and nicotinamide. Biochem J. 1976 May 15;156(2):381–390. doi: 10.1042/bj1560381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Badawy A. A., Smith M. J. Changes in liver tryptophan and tryptophan pyrrolase activity after administration of salicylate and tryptophan to the rat. Biochem Pharmacol. 1972 Jan;21(1):97–101. doi: 10.1016/0006-2952(72)90254-7. [DOI] [PubMed] [Google Scholar]
- Bloxam D. L., Warren W. H. Error in the determination of tryptophan by the method of Denkla and Dewey. A revised procedure. Anal Biochem. 1974 Aug;60(2):621–625. doi: 10.1016/0003-2697(74)90275-9. [DOI] [PubMed] [Google Scholar]
- Bourgoin S., Faivre-Bauman A., Benda P., Glowinski J., Hamon M. Plasma tryptophan and 5-HT metabolism in the CNS of the newborn rat. J Neurochem. 1974 Aug;23(2):319–327. doi: 10.1111/j.1471-4159.1974.tb04361.x. [DOI] [PubMed] [Google Scholar]
- Curzon G., Green A. R. Rapid method for the determination of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in small regions of rat brain. Br J Pharmacol. 1970 Jul;39(3):653–655. doi: 10.1111/j.1476-5381.1970.tb10373.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Curzon G., Knott P. J. Effects on plasma and brain tryptophan in the rat of drugs and hormones that influence the concentration of unesterified fatty acid in the plasma. Br J Pharmacol. 1974 Feb;50(2):197–204. doi: 10.1111/j.1476-5381.1974.tb08562.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Denckla W. D., Dewey H. K. The determination of tryptophan in plasma, liver, and urine. J Lab Clin Med. 1967 Jan;69(1):160–169. [PubMed] [Google Scholar]
- Eccleston D., Ashcroft G. W., Crawford T. B. 5-hydroxyindole metabolism in rat brain. A study of intermediate metabolism using the technique of tryptophan loading. II. Applications and drug studies. J Neurochem. 1965 Jun;12(6):493–503. doi: 10.1111/j.1471-4159.1965.tb06776.x. [DOI] [PubMed] [Google Scholar]
- FEIGELSON P., GREENGARD O. A microsomal iron-porphyrin activator of rat liver tryptophan pyrrolase. J Biol Chem. 1961 Jan;236:153–157. [PubMed] [Google Scholar]
- Frankel D., Khanna J. M., Kalant H., LeBlanc A. E. Effect of acute and chronic ethanol administration on serotonin turnover in rat brain. Psychopharmacologia. 1974 Jun 21;37(4):91–100. doi: 10.1007/BF00437416. [DOI] [PubMed] [Google Scholar]
- Friedman P. A., Kappelman A. H., Kaufman S. Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain. J Biol Chem. 1972 Jul 10;247(13):4165–4173. [PubMed] [Google Scholar]
- Green A. R., Curzon G. Decrease of 5-hydroxytryptamine in the brain provoked by hydrocortisone and its prevention by allopurinol. Nature. 1968 Dec 14;220(5172):1095–1097. doi: 10.1038/2201095a0. [DOI] [PubMed] [Google Scholar]
- Green A. R., Woods H. F., Knott P. G., Curzon G. Letter: Factors influencing effect of hydrocortisone on rat brain tryptophan metabolism. Nature. 1975 May 8;255(5504):170–170. doi: 10.1038/255170a0. [DOI] [PubMed] [Google Scholar]
- Griffiths P. J., Littleton J. M., Ortiz A. Changes in monoamine concentrations in mouse brain associated with ethanol dependence and withdrawal. Br J Pharmacol. 1974 Apr;50(4):489–498. doi: 10.1111/j.1476-5381.1974.tb08582.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamon M., Bourgoin S., Glowinski J. Feedback regulation of 5-HT synthesis in rat striatal slices. J Neurochem. 1973 Jun;20(6):1727–1745. doi: 10.1111/j.1471-4159.1973.tb00288.x. [DOI] [PubMed] [Google Scholar]
- Karobath M., Diaz J. L., Huttunen M. Serotonin synthesis with rat brain synaptosomes. Effects of L-dopa, L-3-methoxytyrosine and catecholamines. Biochem Pharmacol. 1972 May 1;21(9):1245–1251. doi: 10.1016/0006-2952(72)90286-9. [DOI] [PubMed] [Google Scholar]
- Koe B. K. Tryptophan hydroxylase inhibitors. Fed Proc. 1971 May-Jun;30(3):886–896. [PubMed] [Google Scholar]
- Madras B. K., Cohen E. L., Fernstrom J. D., Larin F., Munro H. N., Wurtman R. J. Letter: Dietary carbohydrate increases brain tryptophan and decreases free plasma tryptophan. Nature. 1973 Jul 6;244(5410):34–35. doi: 10.1038/244034a0. [DOI] [PubMed] [Google Scholar]
- Mikac-Dević D., Stanković H., Bosković K. A method for determination of free fatty acids in serum. Clin Chim Acta. 1973 Apr 19;45(1):55–59. doi: 10.1016/0009-8981(73)90144-7. [DOI] [PubMed] [Google Scholar]
- Monroe C. B. Induction of tryptophan oxygenase and tyrosine aminotransferase in mice. Am J Physiol. 1968 Jun;214(6):1410–1414. doi: 10.1152/ajplegacy.1968.214.6.1410. [DOI] [PubMed] [Google Scholar]
- Palaić D., Desaty J., Albert J. M., Panisset J. C. Effect of ethanol on metabolism and subcellular distribution of serotonin in rat brain. Brain Res. 1971 Jan 22;25(2):381–386. doi: 10.1016/0006-8993(71)90445-8. [DOI] [PubMed] [Google Scholar]
- Rawat A. K. Brain levels and turnover rates of presumptive neurotransmitters as influenced by administration and withdrawal of ethanol in mice. J Neurochem. 1974 Jun;22(6):915–922. doi: 10.1111/j.1471-4159.1974.tb04315.x. [DOI] [PubMed] [Google Scholar]
- Tabakoff B., Ritzmann R. F., Boggan W. O. Inhibtion of the transport of 5-hydroxyindoleacetic acid from brain by ethanol. J Neurochem. 1975 May;24(5):1043–1051. doi: 10.1111/j.1471-4159.1975.tb03675.x. [DOI] [PubMed] [Google Scholar]
- Tagliamonte A., Biggio G., Vargiu L., Gessa G. L. Increase of brain tryptophan and stimulation of serotonin synthesis by salicylate. J Neurochem. 1973 Mar;20(3):909–912. doi: 10.1111/j.1471-4159.1973.tb00054.x. [DOI] [PubMed] [Google Scholar]
- Tyce G. M., Flock E. V., Taylor W. F., Owen C. A., Jr Effect of ethanol on 5-hydroxytryptamine turnover in rat brain. Proc Soc Exp Biol Med. 1970 May;134(1):40–44. doi: 10.3181/00379727-134-34723. [DOI] [PubMed] [Google Scholar]
- Yamanaka Y., Kono S. Brain serotonin turnover in alcoholic mice. Jpn J Pharmacol. 1974 Apr;24(2):247–252. [PubMed] [Google Scholar]