Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1972 Sep;69(9):2547–2550. doi: 10.1073/pnas.69.9.2547

Control of Circadian Change of Serotonin N-Acetyltransferase Activity in the Pineal Organ by the β-Adrenergic Receptor

Takeo Deguchi 1, Julius Axelrod 1
PMCID: PMC426985  PMID: 4506772

Abstract

Serotonin N-acetyltransferase (EC 2.3.1.5) activity in the rat pineal organ is enhanced 50-fold at night. Rats exposed to light at night or kept in darkness during the daytime do not show any elevation of enzyme activity. Treatment with reserpine, a compound that depletes norepinephrine from nerves, 1-propranolol, a β-adrenergic blocking agent, or cycloheximide, an inhibitor of protein synthesis, abolishes the nocturnal increase in serotonin N-acetyltransferase activity, indicating that the enzyme activity is modulated by neural release of norepinephrine from sympathetic nerves via β-adrenergic receptors, and that the increase in enzyme activity is due to synthesis of new enzyme molecules. When rats are exposed to light at night or injected with 1-propranolol, there is a precipitous fall in serotonin N-acetyltransferase activity (half-life 5 min). Cycloheximide administered at night results in a slow fall in enzyme activity (half-life 60 min). When rats are kept in darkness and then exposed to light for 10 min, L-isoproterenol rapidly initiates the elevation of serotonin N-acetyltransferase activity to the initial level in 60 min. On the other hand, when the rats are kept in continuous light, L-isoproterenol initiates an increase in serotonin N-acetyltransferase activity after a lag phase of 60 min. The results indicate that there are two types of changes in serotonin N-acetyltransferase activity; a rapid increase and decrease mediated by the β-adrenergic receptor, and a slow increase and decrease in enzyme activity that appears to represent the turnover of the enzyme.

Keywords: diurnal, neural regulation, norepinephrine

Full text

PDF

Selected References

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

  1. AXELROD J., WURTMAN R. J., SNYDER S. H. CONTROL OF HYDROXYINDOLE O-METHYLTRANSFERASE ACTIVITY IN THE RAT PINEAL GLAND BY ENVIRONMENTAL LIGHTING. J Biol Chem. 1965 Feb;240:949–954. [PubMed] [Google Scholar]
  2. Axelrod J., Shein H. M., Wurtman R. J. Stimulation of C14-melatonin synthesis from C14-tryptophan by noradrenaline in rat pineal in organ culture. Proc Natl Acad Sci U S A. 1969 Feb;62(2):544–549. doi: 10.1073/pnas.62.2.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Deguchi T., Axelrod J. Induction and superinduction of serotonin N-acetyltransferase by adrenergic drugs and denervation in rat pineal organ. Proc Natl Acad Sci U S A. 1972 Aug;69(8):2208–2211. doi: 10.1073/pnas.69.8.2208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ebadi M. S., Weiss B., Costa E. Adenosine 3'-5'-monophosphate in rat pineal gland: increase induced by light. Science. 1970 Oct 9;170(3954):188–190. doi: 10.1126/science.170.3954.188. [DOI] [PubMed] [Google Scholar]
  5. Grossman A., Boctor A. Evidence for reversible inactivation of induced tyrosine aminotransferase in rat liver in vivo. Proc Natl Acad Sci U S A. 1972 May;69(5):1161–1164. doi: 10.1073/pnas.69.5.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Klein D. C., Berg G. R., Weller J. Melatonin synthesis: adenosine 3',5'-monophosphate and norepinephrine stimulate N-acetyltransferase. Science. 1970 May 22;168(3934):979–980. doi: 10.1126/science.168.3934.979. [DOI] [PubMed] [Google Scholar]
  7. Klein D. C., Weller J. L. Indole metabolism in the pineal gland: a circadian rhythm in N-acetyltransferase. Science. 1970 Sep 11;169(3950):1093–1095. doi: 10.1126/science.169.3950.1093. [DOI] [PubMed] [Google Scholar]
  8. Klein D. C., Weller J. L., Moore R. Y. Melatonin metabolism: neural regulation of pineal serotonin: acetyl coenzyme A N-acetyltransferase activity. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3107–3110. doi: 10.1073/pnas.68.12.3107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Lynch H. J. Diurnal oscillations in pineal melatonin content. Life Sci I. 1971 Jul 15;10(14):791–795. doi: 10.1016/0024-3205(71)90033-6. [DOI] [PubMed] [Google Scholar]
  11. Neff N. H., Barrett R. E., Costa E. Kinetic and fluorescent histochemical analysis of the serotonin compartments in rat pineal gland. Eur J Pharmacol. 1969 Mar;5(4):348–356. doi: 10.1016/0014-2999(69)90112-5. [DOI] [PubMed] [Google Scholar]
  12. QUAY W. B. CIRCADIAN RHYTHM IN RAT PINEAL SEROTONIN AND ITS MODIFICATIONS BY ESTROUS CYCLE AND PHOTOPERIOD. Gen Comp Endocrinol. 1963 Oct;3:473–479. doi: 10.1016/0016-6480(63)90079-0. [DOI] [PubMed] [Google Scholar]
  13. Volkman P. H., Heller A. Pineal N-acetyltransferase activity: effect of sympathetic stimulation. Science. 1971 Aug 27;173(3999):839–840. doi: 10.1126/science.173.3999.839. [DOI] [PubMed] [Google Scholar]
  14. Wurtman R. J., Axelrod J., Sedvall G., Moore R. Y. Photic and neural control of the 24-hour norepinephrine rhythm in the rat pineal gland. J Pharmacol Exp Ther. 1967 Sep;157(3):487–492. [PubMed] [Google Scholar]
  15. Wurtman R. J., Shein H. M., Larin F. Mediation by -adrenergic receptors of effect of norepinephrine on pineal synthesis of ( 14 C)serotonin and ( 14 C)melatonin. J Neurochem. 1971 Sep;18(9):1683–1687. doi: 10.1111/j.1471-4159.1971.tb03741.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES