Home LiteratureArticle Details
PMID: 240133 Published · ppublish English Journal Article

Tyrosine hydroxylase: allosteric activation induced by stimulation of central noradrenergic neurons.

Naunyn-Schmiedeberg's archives of pharmacology ·Vol. 289 ·No. 4 ·1975-00-00 ·Pages 327-43

Roth RH, Morgenroth VH, Salzman PM

Abstract

Electrical stimulation of the rat locus coeruleus cases about a 300% increase in the activity of the tyrosine hydroxylase prepared from the hippocampus on the stimulated side and assayed in the presence of subsaturating concentrations of tyrosine and pteridine cofactor. Addition of calcium or cAMP to soluble preparations of tyrosine hydroxylase isolated from the hippocampus produces a similar activation of tyrosine hydroxylase. The activation of tyrosine hydroxylase produced by calcium is reversed by addition of the calcium chelator, EGTA, while the activation produced by cAMP addition or by electrical stimulation of the locus coeruleus is unaffected by addition of EGTA to the assay medium. The activation of tyrosine hydroxylase produced by electrical stimulation or by addition of calcium or cAMP to the assay medium appears to be mediated in part by alterations in the kinetic properties of the enzyme. All treatment causes the enzyme to have an increased affinity for substrate and pteridine cofactor and a decreased affinity for the endproduct inhibitor, norepinephrine. These results are suggestive that the activation of tyrosine hydroxylase which occurs during periods of increased impulse flow in noradrenergic neurons may be initiated by alterations in calcium fluxes or by changes in the steady state levels of cAMP which accompany neuronal depolarization.

MeSH Terms
Allosteric Regulation/drug effects Animals Biopterin Calcium/pharmacology Cations, Divalent/pharmacology Cerebral Ventricles/physiology Cyclic AMP/pharmacology Egtazic Acid/pharmacology Electric Stimulation Enzyme Activation/drug effects Hippocampus/enzymology Kinetics Male Neurons/enzymology,physiology Norepinephrine/physiology Phosphates/metabolism Rats Sympathetic Nervous System/physiology Tyrosine 3-Monooxygenase/metabolism
Chemicals
Cations, Divalent Phosphates Biopterin Egtazic Acid Cyclic AMP Tyrosine 3-Monooxygenase Calcium Norepinephrine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Roth R H
Morgenroth V H
Salzman P M
References (29)
29 references, click to expand
  1. Statistical estimations in enzyme kinetics.
    Biochem J. 1961 Aug;80:324-32 PMID: 13785321
  2. Factors influencing the rate of norepinephrine biosynthesis in nerve tissue.
    J Pharmacol Exp Ther. 1967 Dec;158(3):373-7 PMID: 4965285
  3. Tyrosine hydroxylase: activation by nerve stimulation.
    Proc Natl Acad Sci U S A. 1974 Nov;71(11):4283-7 PMID: 4155067
  4. Comparison of the effects of Ca 2+ and Mg 2+ on the adenyl cyclase of beef brain.
    Biochim Biophys Acta. 1972 Aug 28;276(2):434-43 PMID: 4341589
  5. The determination of enzyme inhibitor constants.
    Biochem J. 1953 Aug;55(1):170-1 PMID: 13093635
  6. Alterations in turnover and endogenous levels of norepinephrine in cerebral cortex following electrical stimulation and acute axotomy of cerebral noradrenergic pathways.
    Eur J Pharmacol. 1973 Sep;23(3):276-82 PMID: 4583563
  7. Cyclic nucleotide-dependent protein kinases. IV. Widespread occurrence of adenosine 3',5'-monophosphate-dependent protein kinase in various tissues and phyla of the animal kingdom.
    Proc Natl Acad Sci U S A. 1969 Dec;64(4):1349-55 PMID: 4393915
  8. Effect of membrane depolarization and biogenic amines on the formation of cyclic AMP in incubated brain slices.
    Adv Biochem Psychopharmacol. 1970;3:135-54 PMID: 4331454
  9. Inhibitors of purified beef adrenal tyrosine hydroxylase.
    Biochem Pharmacol. 1965 May;14(5):837-45 PMID: 5840732
  10. Acceleration of norepinephrine synthesis in the rat submaxillary gland in vivo during sympathetic nerve stimulation.
    Life Sci. 1967 Jan 1;6(1):45-51 PMID: 6030556
  11. Cyclic adenosine 3',5'-monophosphate formation in brain slices: stimulation by batrachotoxin, ouabain, veratridine, and potassium ions.
    Mol Pharmacol. 1970 Mar;6(2):184-8 PMID: 4313865
  12. Acceleration of noradrenaline biosynthesis by nerve stimulation.
    Life Sci. 1966 Jun;5(12):1071-5 PMID: 4960408
  13. Noradrenergic neurons: allosteric activation of hippocampal tyrosine hydroxylase by stimulation of the locus coeruleus.
    Biochem Pharmacol. 1974 Oct 1;23(19):2779-84 PMID: 4153688
  14. TYROSINE HYDROXYLASE. THE INITIAL STEP IN NOREPINEPHRINE BIOSYNTHESIS.
    J Biol Chem. 1964 Sep;239:2910-7 PMID: 14216443
  15. The effect of electrical stimulation upon the accumulation of adenosine 3',5'-phosphate in isolated cerebral tissue.
    J Neurochem. 1969 Apr;16(4):485-91 PMID: 4388774
  16. Increased synthesis of norepinephrine in the rat heart on electrical stimulation of the stellate ganglia.
    Mol Pharmacol. 1966 Nov;2(6):610-3 PMID: 5965327
  17. Regulation of norepinephrine biosynthesis.
    Annu Rev Pharmacol. 1970;10:273-90 PMID: 4315686
  18. Activation by cyclic 3':5'-adenosine monophosphate of tyrosine hydroxylase in the rat brain.
    Proc Natl Acad Sci U S A. 1975 Mar;72(3):789-93 PMID: 236558
  19. Tyrosine hydroxylase in rat brain--cofactor requirements, regional and subcellular distribution.
    Biochem Pharmacol. 1972 Jul 15;21(14):1935-44 PMID: 4405450
  20. Evidence for involvement of protein kinase in the activation by adenosine 3':5'-monophosphate of brain tyrosine 3-monooxygenase.
    J Biol Chem. 1975 Mar 10;250(5):1946-8 PMID: 234470
  21. Catecholamine and Ca 2+ activation of adenylate cyclase systems in synaptosomal fractions from rat cerebral cortex.
    Nat New Biol. 1973 Mar 14;242(115):58-60 PMID: 4348576
  22. Transport and metabolism of calcium ions in nerve.
    Prog Biophys Mol Biol. 1972;24:177-223 PMID: 4118937
  23. Solubilization and partial purification of tyrosine hydroxylase from bovine adrenal medulla.
    J Biol Chem. 1971 Mar 10;246(5):1330-40 PMID: 5545077
  24. Regulation of catecholamine synthesis in the rat brain in vitro by cyclic AMP.
    Nature. 1974 Nov 8;252(5479):156-8 PMID: 4153840
  25. The role of calcium in the release of neurotransmitter substances and hormones.
    Pharmacol Rev. 1970 Sep;22(3):389-428 PMID: 4322219
  26. Protein measurement with the Folin phenol reagent.
    J Biol Chem. 1951 Nov;193(1):265-75 PMID: 14907713
  27. The regulation of norepinephrine synthesis in sympathetic nerves: effect of nerve stimulation, cocaine, and catecholamine-releasing agents.
    Proc Natl Acad Sci U S A. 1966 Nov;56(5):1491-6 PMID: 4382063
  28. Further studies on the increased synthesis of norepinephrine during nerve stimulation of guinea-pig vas deferens preparation: effect of tyrosine and 6, 7-dimethyltetrahydropterin.
    J Pharmacol Exp Ther. 1973 Jul;186(1):75-85 PMID: 4723315
  29. Identification of a calcium-binding protein as a calcium-dependent regulator of brain adenylate cyclase.
    Proc Natl Acad Sci U S A. 1975 Jan;72(1):64-8 PMID: 164029
Article Info
Journal
Naunyn-Schmiedeberg's archives of pharmacology
Abbr.
Naunyn Schmiedebergs Arch Pharmacol
ISSN
0028-1298
DOI
10.1007/BF00508408
Published
1975-00-00
Pages
327-43
Language
English
Region
Germany
NLM ID
0326264
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00508408 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2