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Molecular Pharmacology

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Research ArticleArticle

Potassium-Induced Acceleration of Catecholamine Biosynthesis in Brain Slices

I. A Study on the Mechanism of Action

JANE E. HARRIS and ROBERT H. ROTH
Molecular Pharmacology November 1971, 7 (6) 593-604;
JANE E. HARRIS
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

Incubation of cortical or striatal slices in a K+-enriched medium (53 mM) enhanced the release of newly synthesized catecholamines and accelerated the synthesis of catecholamines at the rate-limiting tyrosine hydroxylase step. The specific activity of the 14C-tyrosine found in the tissues after incubation in a K+-enriched medium was similar to that of control tissues. Thus the enhancement of catecholamine synthesis observed in the K+-enriched medium did not appear to arise from an increase in the specific activity of the precursor. No evidence was obtained for any alteration in the level of tyrosine hydroxylase activity in homogenates of tissues previously incubated in a K+-enriched medium. Conditions which block the release of catecholamines, such as absence of calcium or high magnesium concentrations, blocked the release of newly synthesized catecholamines and simultaneously antagonized the K+-induced acceleration of catecholamine biosynthesis. On the other hand, the catecholamine synthesis rate of tissues incubated in normal Krebs-Ringer-phosphate buffer was enhanced by initial incubation of the slices in a K+-enriched medium. Furthermore, when catecholamines were added to the medium at a concentration as low as 10-7 M, the catecholamine synthesis rate was inhibited; this inhibition occurred intraneuronally, since the inhibitory effect of exogenous norepinephrine was antagonized by cocaine, even under conditions in which tissue levels of exogenous amines remained the same. These results support the hypothesis that neuronal depolarization enhances the release of newly formed catecholamines, which, in turn, relieves the rate-limiting enzyme, tyrosine hydroxylase, from end-product inhibition and thereby accelerates the catecholamine synthesis rate.

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Molecular Pharmacology
Vol. 7, Issue 6
1 Nov 1971
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Research ArticleArticle

Potassium-Induced Acceleration of Catecholamine Biosynthesis in Brain Slices

JANE E. HARRIS and ROBERT H. ROTH
Molecular Pharmacology November 1, 1971, 7 (6) 593-604;

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Research ArticleArticle

Potassium-Induced Acceleration of Catecholamine Biosynthesis in Brain Slices

JANE E. HARRIS and ROBERT H. ROTH
Molecular Pharmacology November 1, 1971, 7 (6) 593-604;
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