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Molecular Pharmacology

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Research ArticleArticle

Activation of Tyrosine Hydroxylase from Central Noradrenergic Neurons by Calcium

VICTOR H. MORGENROTH III, MARGARET C. BOADLE-BIBER and ROBERT H. ROTH
Molecular Pharmacology July 1975, 11 (4) 427-435;
VICTOR H. MORGENROTH III
Departments of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510
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MARGARET C. BOADLE-BIBER
Departments of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510
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ROBERT H. ROTH
Departments of Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510
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Abstract

Addition of CaCl2 to soluble preparations of tyrosine hydroxylase from rat medulla pons produces a marked activation of the enzyme assayed with subsaturating concentrations of tyrosine (10 µM) and pteridine cofactor (2-amino-4-hydroxy-6,7-dimethyl-5,6,7,8-tetrahydropteridine, 100 µM). While some increase in activity occurs with Ca++ concentrations as low as 10 µM, activation is maximal at 50 µM Ca++ and remains unchanged up to 1.0 mM. BaC12 produces similar although less pronounced effects. MgCl2 prevents the activation of the enzyme if added to the reaction mixture before CaCl2. Alone MgCl2 has no effect in concentrations up to 1 mM. Ethylene glycol bis(β-aminoethyl ether)-N,N'-tetraacetic acid has no direct effects on the enzyme but completely antagonizes the activation produced by Ca++. The activation of tyrosine hydroxylase by Ca++ is reflected in changes in the kinetic properties of the enzyme. The Km for tyrosine decreases from 58.1 to 10.3 µM, the Km for pteridine cofactor decreases from 673 to 125 µM, and the Ki for norepinephrine increases almost 20-fold, from 0.34 to 6.27 mM, in the presence of Ca++. Thus norepinephrine is a much less effective inhibitor of the Ca++-activated enzyme. The proposal is made that Ca++ which enters the nerve terminal during nerve stimulation may enhance norepinephrine synthesis by activating tyrosine hydroxylase in a manner similar to the activation observed in vitro with CaCl2. Similar findings are reported for tyrosine hydroxylase isolated from rat cerebral cortex.

ACKNOWLEDGMENTS Thanks are due to Ms. Ilona Decerbo and Ms. Anne Morrison for their excellent technical assistance.

  • Copyright ©, 1975, by Academic Press, Inc.

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Molecular Pharmacology
Vol. 11, Issue 4
1 Jul 1975
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Research ArticleArticle

Activation of Tyrosine Hydroxylase from Central Noradrenergic Neurons by Calcium

VICTOR H. MORGENROTH, MARGARET C. BOADLE-BIBER and ROBERT H. ROTH
Molecular Pharmacology July 1, 1975, 11 (4) 427-435;

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Research ArticleArticle

Activation of Tyrosine Hydroxylase from Central Noradrenergic Neurons by Calcium

VICTOR H. MORGENROTH, MARGARET C. BOADLE-BIBER and ROBERT H. ROTH
Molecular Pharmacology July 1, 1975, 11 (4) 427-435;
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