Skip to main content
Log in

Tyrosine hydroxylase activity increases in pineal sympathetic nerves after depletion of neuronal serotonin

  • Short Communication
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The injection of p-chlorophenylalanine (PCPA) acutely reduced serotonin in the pineal gland of the rat and selectively elevated the noradrenaline (NA) content during the subsequent 24 h. The activity of tyrosine hydroxylase (TH) also increased in intact glands during the first 6 h after PCPA injection but returned to normal at 24 h. This enhancement of enzyme activity was only observed in the presence of a non-saturating concentration of the cofactor. Serotonin depletion by PCPA cannot directly account for the increased enzyme activity, because the amine does not modify TH activity. Moreover, this increase is restricted to the pineal, since in other sympathetically innervated organs, such as the atria, PCPA produced an acute but transient reduction in TH activity. The elevation described here is not due to a net increase in the amount of enzymatic protein, because TH activity is similar in pineal homogenates from treated and control rats when a saturating concentration of the cofactor was used. The availability of storage sites in pineal nerve vesicles due to serotonin depletion, seems to release TH activity from the negative control exerted by cytoplasmic catecholamines. Enzyme activity in the pineal is acutely enhanced until a new steady state is reached at a higher concentration of endogenous NA.

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.

References

  • Atack, C.: The determination of dopamine by a modification of the dihydroxyindole fluorometric assay. Br. J. Pharmacol. 48, 699–714 (1973)

    Google Scholar 

  • Atack, C., Magnusson, T.: Individual elution of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from a single, strong cation exchange column, by means of mineral acid-organic solvent mixtures. J. Pharm. Pharmacol. 22, 625–627 (1970)

    Google Scholar 

  • Axelrod, J.: The pineal gland: a neurochemical transducer. Science 184, 1341–1348 (1974)

    Google Scholar 

  • Brownstein, M.: The pineal gland. Life Sci. 16, 1363–1374 (1975)

    Google Scholar 

  • Brownstein, M., Axelrod, J.: Pinal gland: 24-hour rhythm in norepinephrine turnover. Science 184, 163–165 (1974)

    Google Scholar 

  • Deguchi, T., Barchas, J.: Effect of p-chlorophenylalanine on hydroxylation of tryptophan in pineal and brain of rats. Mol. Pharmacol. 8, 770–779 (1972)

    Google Scholar 

  • Häggendal, J.: An improved method for the fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissues. Acta Physiol. Scand. 59, 242–254 (1963)

    Google Scholar 

  • Jaim-Etcheverry, G., Zieher, L. M.: Ultrastructural cytochemistry and pharmacology of 5-hydroxytryptamine in adrenergic nerve endings. III. Selective increase of norepinephrine in the rat pineal gland consecutive to depletion of neuronal 5-hydroxytryptamine. J. Pharmacol. Exp. Ther. 178, 42–48 (1971)

    Google Scholar 

  • Jaim-Etcheverry, G., Zieher, L. M.: Octopamine probably coexists with noradrenaline and serotonin in vesicles of pineal adrenergic nerves. J. Neurochem. 25, 915–917 (1975a)

    Google Scholar 

  • Jaim-Etcheverry, G., Zieher, L. M.: Stimulation of beta-adrenergic receptors in the pineal gland increases the noradrenaline stores of its sympathetic nerves. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 425–431 (1975b)

    Google Scholar 

  • Klein, D. C.: Circadian rhythms in indole metabolism in the rat pineal gland. In: The neurosciences (F. O. Schmitt and F. G. Worden, eds.). Third Study Program, p. 509. Cambridge. Mass.: The MIT Press 1974

    Google Scholar 

  • Koe, B. K., Weissman, A.: p-Chlorophenylalanine, a specific depletor of brain serotonin. J. Pharmacol. Exp. Ther. 154, 499–516 (1966)

    Google Scholar 

  • Magnusson, T.: Effect of chronic transection on dopamine, noradrenaline and 5-hydroxytryptamine in the rat spinal cord. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 13–22 (1973)

    Google Scholar 

  • McGeer, E. G., McGeer, P. L.: Circadian rhythm in pineal tyrosine hydroxylase. Science 153, 73–74 (1966)

    Google Scholar 

  • Nagatsu, T., Levitt, M., Udenfriend, S.: Tyrosine hydroxylase. The initial step in norepinephrine biosynthesis. J. Biol. Chem. 239, 2910–2917 (1964)

    Google Scholar 

  • Rubio, M. C.: Regulatory mechanisms for the enzymes involved in the synthesis of noradrenaline under different experimental conditions. Gen. Pharmacol. 7, 153–157 (1976)

    Google Scholar 

  • Spector, S., Gordon, R., Sjoerdsma, A., Udenfriend, S.: End-product inhibition of tyrosine hydroxylase as a possible mechanism for regulation of norepinephrine synthesis. Mol Pharmacol. 3, 549–555 (1967)

    Google Scholar 

  • Udenfriend, S., Zaltzman-Nirenberg, P., Nagatsu, T.: Inhibitors of purified beef adrenal tyrosine hydroxylase. Biochem. Pharmacol. 14, 837–845 (1965)

    Google Scholar 

  • Waymire, J. C., Bjur, R., Weiner, N.: Assay of tyrosine hydroxylase by coupled decarboxylation of Dopa formed from l-14C-L-tyrosine. Anal. Biochem. 43, 588–600 (1971)

    Google Scholar 

  • Weiner, N.: Regulation of norepinephrine biosynthesis. Ann. Rev. Pharmacol. 10, 273–290 (1970)

    Google Scholar 

  • Weiner, N., Cloutier, G., Bjur, R., Pfeffer, R. I.: Modification of norepinephrine synthesis in intact tissue by drugs and during short term adrenergic nerve stimulation. Pharmacol. Rev. 24, 203–221 (1972)

    Google Scholar 

  • Zhelyaskov, D. H., Levitt, M., Udenfriend, S.: Tryptophan derivatives as inhibitors of tyrosine hydroxylase in vivo and in vitro. Mol. Pharmacol. 4, 445–451 (1968)

    Google Scholar 

  • Zweig, M., Axelrod, J.: Relationship between catecholamines and serotonin in sympathetic nerves of the rat pineal gland. J. Neurobiol. 1, 87–97 (1969)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rubio, M.C., Jaim-Etcheverry, G. & Zieher, L.M. Tyrosine hydroxylase activity increases in pineal sympathetic nerves after depletion of neuronal serotonin. Naunyn-Schmiedeberg's Arch. Pharmacol. 301, 75–78 (1977). https://doi.org/10.1007/BF00501266

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00501266

Key words

Navigation