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

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 t...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 1975-01, Vol.289 (4), p.327-343
Main Authors: Roth, R H, Morgenroth, 3rd, V H, Salzman, P M
Format: Article
Language:English
Subjects:
Allosteric Regulation - drug effects
Animals
Biopterins
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
Neurons - physiology
Norepinephrine - physiology
Phosphates - metabolism
Rats
Sympathetic Nervous System - physiology
Tyrosine 3-Monooxygenase - metabolism
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Summary: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.
ISSN:0028-1298
1432-1912
DOI:10.1007/BF00508408