Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1973 Jul;134(3):763–767. doi: 10.1042/bj1340763

Effects of pyridoxine deficiency and dl-p-chlorophenylalanine administration to rats on 5-hydroxytryptamine and noradrenaline concentrations in brain and 5-hydroxytryptamine concentration in blood

Hemmige N Bhagavan 1, David B Coursin 1
PMCID: PMC1177873  PMID: 4270682

Abstract

Pyridoxine deficiency in post-weanling rats caused a marked decrease in body weight and a small but significant decrease in brain weight. Although the concentration of circulating 5-hydroxytryptamine was markedly decreased, the concentrations of 5-hydroxytryptamine and noradrenaline in the brain were not affected. p-Chlorophenylalanine, an inhibitor of 5-hydroxytryptamine synthesis, decreased the 5-hydroxytryptamine content of brain to very low values in both the deficient and control animals, whereas the noradrenaline contents were not appreciably affected. The concentration of 5-hydroxytryptamine in blood, the origin of which is primarily gastrointestinal, was decreased only in the controls but not in the deficient animals after p-chlorophenylalanine treatment. These results suggest that whereas l-tryptophan hydroxylase (EC 1.14.3.2) is rate-limiting in the brain as has been reported by others, the pyridoxal 5′-phosphate-dependent enzyme 5-hydroxytryptophan decarboxylase (EC 4.1.1.28) may be more important in the gastrointestinal tract in the regulation of 5-hydroxytryptamine synthesis.

Full text

PDF
763

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bhagavan H. N., Coursin D. B. Effect of pyridoxine deficiency on nucleic acid and protein contents of brain and liver in rats. Int J Vitam Nutr Res. 1971;41(3):419–423. [PubMed] [Google Scholar]
  2. Bhagavan H. N., Coursin D. B. In vivo incorporation of L-(U- 14 C) lysine and L-(U- 14 C) leucine into brain proteins in pyridoxine deficiency. Int J Vitam Nutr Res. 1971;41(2):231–239. [PubMed] [Google Scholar]
  3. Bhagavan H. N., Coursin D. B., Stewart C. N. Monosodium glutamate induces convulsive disorders in rats. Nature. 1971 Jul 23;232(5308):275–276. doi: 10.1038/232275a0. [DOI] [PubMed] [Google Scholar]
  4. Brody J. F., Jr Behavioral effects of serotonin depletion and of p-chlorophenylalanine (a serotonin depletor) in rats. Psychopharmacologia. 1970;17(1):14–33. doi: 10.1007/BF00402088. [DOI] [PubMed] [Google Scholar]
  5. DAVIS V. E. Effect of cortisone and thyroxine on aromatic amino acid decarboxylation. Endocrinology. 1963 Jan;72:33–38. doi: 10.1210/endo-72-1-33. [DOI] [PubMed] [Google Scholar]
  6. Dakshinamurti K., Stephens M. C. Pyridoxine deficiency in the neonatal rat. J Neurochem. 1969 Nov;16(11):1515–1522. doi: 10.1111/j.1471-4159.1969.tb09906.x. [DOI] [PubMed] [Google Scholar]
  7. Eberle E. D., Eiduson S. Effect of pyridoxine deficiency on aromatic L-amino acid decarboxylase in the developing rat liver and brain. J Neurochem. 1968 Oct;15(10):1071–1083. doi: 10.1111/j.1471-4159.1968.tb06825.x. [DOI] [PubMed] [Google Scholar]
  8. Fernstrom J. D., Wurtman R. J. Brain serotonin content: physiological dependence on plasma tryptophan levels. Science. 1971 Jul 9;173(3992):149–152. doi: 10.1126/science.173.3992.149. [DOI] [PubMed] [Google Scholar]
  9. Jéquier E., Lovenberg W., Sjoerdsma A. Tryptophan hydroxylase inhibition: the mechanism by which p-chlorophenylalanine depletes rat brain serotonin. Mol Pharmacol. 1967 May;3(3):274–278. [PubMed] [Google Scholar]
  10. Koe B. K. Tryptophan hydroxylase inhibitors. Fed Proc. 1971 May-Jun;30(3):886–896. [PubMed] [Google Scholar]
  11. Koe B. K., Weissman A. p-Chlorophenylalanine: a specific depletor of brain serotonin. J Pharmacol Exp Ther. 1966 Dec;154(3):499–516. [PubMed] [Google Scholar]
  12. Maruyama H., Coursin D. B. Enzymic assay of pyridoxal phosphate using tyrosine apodecarboxylase and tyrosine-1-14C. Anal Biochem. 1968 Dec;26(3):420–429. doi: 10.1016/0003-2697(68)90203-0. [DOI] [PubMed] [Google Scholar]
  13. McGeer E. G., Peters D. A., McGeer P. L. Inhibition of rat brain tryptophan hydroxylase by 6-halotryptophans. Life Sci. 1968 Jun 15;7(12):605–615. doi: 10.1016/0024-3205(68)90082-9. [DOI] [PubMed] [Google Scholar]
  14. Moir A. T., Eccleston D. The effects of precursor loading in the cerebral metabolism of 5-hydroxyindoles. J Neurochem. 1968 Oct;15(10):1093–1108. doi: 10.1111/j.1471-4159.1968.tb06827.x. [DOI] [PubMed] [Google Scholar]
  15. Schlesinger K., Schreiber R. A. Interaction of drugs and pyridoxine deficiency on central nervous system excitability. Ann N Y Acad Sci. 1969 Sep 30;166(1):281–287. doi: 10.1111/j.1749-6632.1969.tb54278.x. [DOI] [PubMed] [Google Scholar]
  16. Shellenberger M. K., Gordon J. H. A rapid, simplified procedure for simultaneous assay of norepinephrine, dopamine, and 5-hydroxytryptamine from discrete brain areas. Anal Biochem. 1971 Feb;39(2):356–372. doi: 10.1016/0003-2697(71)90426-x. [DOI] [PubMed] [Google Scholar]
  17. Sourkes T. L., Missala K. Metabolism of dihydroxyphenylalanine and tryptophan in pyridoxine-deficient rats. Ann N Y Acad Sci. 1969 Sep 30;166(1):235–245. doi: 10.1111/j.1749-6632.1969.tb54274.x. [DOI] [PubMed] [Google Scholar]
  18. Tagliamonte A., Tagliamonte P., Perez-Cruet J., Gessa G. L. Increase of brain tryptophan caused by drugs which stimulate serotonin synthesis. Nat New Biol. 1971 Jan 27;229(4):125–126. doi: 10.1038/newbio229125a0. [DOI] [PubMed] [Google Scholar]
  19. WEBER F., WISS O. [On the distinct influence of vitamin B6 deficiency on tryptophan metabolism in the rat]. Hoppe Seylers Z Physiol Chem. 1963 Mar;331:124–131. doi: 10.1515/bchm2.1963.331.1.124. [DOI] [PubMed] [Google Scholar]
  20. WISS O., WEBER F. BIOCHEMICAL PATHOLOGY OF VITAMIN B6 DEFICIENCY. Vitam Horm. 1964;22:495–501. doi: 10.1016/s0083-6729(08)60350-7. [DOI] [PubMed] [Google Scholar]
  21. Welch A. S., Welch B. L. Solvent extraction method for simultaneous determination of norepinephrine, dopamine, serotonin, and 5-hydroxyindoleacetic acid in a single mouse brain. Anal Biochem. 1969 Aug;30(2):161–179. doi: 10.1016/0003-2697(69)90387-x. [DOI] [PubMed] [Google Scholar]
  22. Yuwiler A., Plotkin S., Geller E., Ritvo E. R. A rapid accurate procedure for the determination of serotonin in whole human blood. Biochem Med. 1970 Apr;3(5):426–431. doi: 10.1016/0006-2944(70)90010-4. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES