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Related Experiment Videos

Tyrosine hydroxylase: activation by nerve stimulation.

V H Morgenroth, M Boadle-Biber, R H Roth

    Proceedings of the National Academy of Sciences of the United States of America
    |November 1, 1974
    PubMed
    Summary

    Electrical stimulation increases norepinephrine synthesis by activating tyrosine hydroxylase (TH). Calcium ions (Ca++) play a key role in this TH activation, mimicking nerve stimulation effects and enhancing neurotransmitter formation.

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    Area of Science:

    • Neuroscience
    • Biochemistry
    • Pharmacology

    Background:

    • Norepinephrine synthesis is accelerated by electrical stimulation in the guinea pig vas deferens.
    • The underlying molecular mechanism for enhanced norepinephrine formation is not fully understood.
    • Increased activity of tyrosine hydroxylase (TH) during nerve stimulation has been proposed.

    Purpose of the Study:

    • To investigate the molecular mechanism of enhanced norepinephrine synthesis during nerve stimulation.
    • To determine the role of tyrosine hydroxylase (TH) activity in this process.
    • To explore the involvement of calcium ions (Ca++) in TH activation.

    Main Methods:

    • Isolated crude tyrosine hydroxylase (TH) preparations from electrically stimulated or potassium-depolarized guinea pig vasa deferentia.

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  • Assay of TH activity in the presence and absence of calcium ions (Ca++) and EGTA.
  • Analysis of kinetic properties of TH, including substrate and cofactor affinity, and end-product inhibition.
  • Main Results:

    • Electrically stimulated or potassium-depolarized tissues showed increased TH activity compared to controls.
    • Increased TH activity was partially antagonized by EGTA and blocked by Ca++ removal.
    • Addition of Ca++ to isolated TH activated the enzyme, an effect reversed by EGTA.
    • Activation of TH by Ca++ or stimulation involved increased affinity for substrate/cofactor and decreased affinity for norepinephrine.

    Conclusions:

    • Enhanced norepinephrine formation during nerve stimulation results from tyrosine hydroxylase (TH) activation.
    • Calcium ions (Ca++) are directly involved in the activation of TH.
    • Nerve stimulation-induced Ca++ influx or mobilization may mediate TH activation, linking it to neurotransmitter release.