Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1985 Jul;85(3):591–598. doi: 10.1111/j.1476-5381.1985.tb10553.x

Evidence that the accumulation of 5-hydroxytryptamine in the liver but not in the brain may cause the hypoglycaemia induced by 5-hydroxytryptophan.

Y Endo
PMCID: PMC1916514  PMID: 3875380

Abstract

Experiments were undertaken to determine whether the site of the hypoglycaemic action of 5-hydroxytryptophan (5-HTP), a direct precursor of 5-hydroxytryptamine (5-HT), was in the central nervous system or in the liver. The fall in blood glucose followed the rapid increase in the amount of 5-HT both in the brain and liver after 5-HTP injection into pargyline-treated and non-treated mice. Carbidopa, an inhibitor of peripheral aromatic amino acid decarboxylase, prevented the elevation of 5-HT levels in the liver of both pargyline-treated and non-treated mice. In contrast, carbidopa did not prevent but rather enhanced the elevation of 5-HT levels in the brain of both groups of mice. Corresponding to the prevention of 5-HT elevation in the liver, the fall in blood glucose was prevented by carbidopa. These results support the idea that the accumulation of 5-HT in the liver but not in the brain causes the hypoglycaemia induced by 5-HTP.

Full text

PDF
591

Selected References

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

  1. Darwish S. A., Furman B. L. Medication of the hypoglycaemic effect of 5-hydroxytryptophan by a central nervous system action. Experientia. 1974 Nov 15;30(11):1306–1307. doi: 10.1007/BF01945199. [DOI] [PubMed] [Google Scholar]
  2. Endo Y. A lipopolysaccharide and concanavalin A induce variations of serotonin levels in mouse tissues. Eur J Pharmacol. 1983 Aug 5;91(4):493–499. doi: 10.1016/0014-2999(83)90175-9. [DOI] [PubMed] [Google Scholar]
  3. Endo Y. Induction of hypoglycaemia and accumulation of 5-hydroxytryptamine in the liver after the injection of mitogenic substances into mice. Br J Pharmacol. 1984 Apr;81(4):645–650. doi: 10.1111/j.1476-5381.1984.tb16130.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Filkins J. P., Cornell R. P. Depression of hepatic gluconeogenesis and the hypoglycemia of endotoxin shock. Am J Physiol. 1974 Oct;227(4):778–781. doi: 10.1152/ajplegacy.1974.227.4.778. [DOI] [PubMed] [Google Scholar]
  5. Furman B. L. The hypoglycaemic effect of 5-hydroxytryptophan. Br J Pharmacol. 1974 Apr;50(4):575–580. doi: 10.1111/j.1476-5381.1974.tb08591.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Furman B. L., Wilson G. A. Further studies on the effects of 5-hydroxytryptophan on plasma glucose and insulin in the mouse. Diabetologia. 1980 Oct;19(4):386–390. doi: 10.1007/BF00280525. [DOI] [PubMed] [Google Scholar]
  7. Lloyd P., Smith S. A., Stribling D., Pogson C. I. Factors affecting tryptophan-induced hypoglycaemia in rats. Biochem Pharmacol. 1982 Nov 15;31(22):3563–3569. doi: 10.1016/0006-2952(82)90576-7. [DOI] [PubMed] [Google Scholar]
  8. Lloyd P., Stribling D., Pogson C. I. Endotoxin and tryptophan-induced hypoglycaemia in rats. Biochem Pharmacol. 1982 Nov 15;31(22):3571–3576. doi: 10.1016/0006-2952(82)90577-9. [DOI] [PubMed] [Google Scholar]
  9. Lundquist I., Ekholm R., Ericson L. E. Monoamines in the pancreatic islets of the mouse. 5-hydroxytryptamine as an intracellular modifier of insulin secretion, and the hypoglycaemic action of monoamine oxidase inhibitors. Diabetologia. 1971 Dec;7(6):414–422. doi: 10.1007/BF01212056. [DOI] [PubMed] [Google Scholar]
  10. McCallum R. E., Berry L. J. Effects of endotoxin on gluconeogenesis, glycogen synthesis, and liver glycogen synthase in mice. Infect Immun. 1973 Apr;7(4):642–654. doi: 10.1128/iai.7.4.642-654.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ray P. D., Hanson R. L., Lardy H. A. Inhibition by hydrazine of gluconeogenesis in the rat. J Biol Chem. 1970 Feb 25;245(4):690–696. [PubMed] [Google Scholar]
  12. Smith P. H., Porte D., Jr Neuropharmacology of the pancreatic islets. Annu Rev Pharmacol Toxicol. 1976;16:269–285. doi: 10.1146/annurev.pa.16.040176.001413. [DOI] [PubMed] [Google Scholar]
  13. Smith S. A., Carr F. P., Pogson C. I. The metabolism of L-tryptophan by isolated rat liver cells. Quantification of the relative importance of, and the effect of nutritional status on, the individual pathways of tryptophan metabolism. Biochem J. 1980 Nov 15;192(2):673–686. doi: 10.1042/bj1920673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Smith S. A., Elliott K. R., Pogson C. I. Differential effects of tryptophan on glucose synthesis in rats and guinea pigs. Biochem J. 1978 Dec 15;176(3):817–825. doi: 10.1042/bj1760817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Smith S. A., Elliott K. R., Pogson C. I. Inhibition of hepatic gluconeogenesis by tryptophan metabolites in rats and guinea pigs. Biochem Pharmacol. 1979 Jul 15;28(14):2145–2148. doi: 10.1016/0006-2952(79)90196-5. [DOI] [PubMed] [Google Scholar]
  16. Smith S. A., Pogson C. L. Tryptophan and the control of plasma glucose concentrations in the rat. Biochem J. 1977 Dec 15;168(3):495–506. doi: 10.1042/bj1680495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tadano T., Endo Y., Kisara K. A simple determination of serotonin, 5-hydroxyindoleacetic acid and 5-hydroxytryptophan decarboxylase activity in rat brain areas and parallel correlation among the levels. Jpn J Pharmacol. 1980 Jun;30(3):347–356. doi: 10.1254/jjp.30.347. [DOI] [PubMed] [Google Scholar]
  18. UDENFRIEND S., WEISSBACH H., BOGDANSKI D. F. Increase in tissue serotonin following administration of its precursor 5-hydroxytryptophan. J Biol Chem. 1957 Feb;224(2):803–810. [PubMed] [Google Scholar]
  19. Warsh J. J., Stancer H. C. Brain and peripheral metabolism of 5-hydroxytryptophan-14C following peripheral decarboxylase inhibition. J Pharmacol Exp Ther. 1976 Jun;197(3):545–555. [PubMed] [Google Scholar]
  20. Wilson G. A., Furman B. L. Effects of inhibitors of 5-hydroxytryptamine uptake on plasma glucose and their interaction with 5-hydroxytryptophan in producing hypoglycaemia in mice. Eur J Pharmacol. 1982 Mar 12;78(3):263–270. doi: 10.1016/0014-2999(82)90027-9. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES