Tyrosine hydroxylase regulation in the central nervous system

Masserano, Joseph M.; Weiner, Norman

doi:10.1007/bf00225250

Cited by 58 publications

(17 citation statements)

References 140 publications

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“…3). This finding agrees with those of Weiner et al (26) in crude striatal supernatant as well as those of Masserano and Weiner (27) in crude adrenal supernatant. In the previous studies, in which the effect of cAMP and ATP/Mg2+ on enzyme activity was examined, no change in enzyme Vma.…”

Section: Methodssupporting

confidence: 94%

Evidence for the involvement of a cyclic AMP-independent protein kinase in the activation of soluble tyrosine hydroxylase from rat striatum.

Andrews¹,

Langan²,

Weiner³

1983

Proc. Natl. Acad. Sci. U.S.A.

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Activation of rat striatal tyrosine hydroxylase [TyrOHase; tyrosine monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] by ATP/Mg2+ and endogenous protein kinase can be produced without the addition of cAMP. This activation is not due to endogenous free catalytic subunit derived from cAMP-dependent protein kinase. In the presence of amounts of protein kinase inhibitor sufficient for complete inhibition of striatal cAMP-dependent protein kinase and the cAMP-mediated activation of TyrOHase, addition of ATP/Mg2+ results in an enhancement of TyrOHase activity. Enzyme activation does not occur when the nonhydrolyzable form of ATP, adenylyl imidodiphosphate, is substituted for ATP. When TyrOHase is assayed in the presence of ATP/Mg2+ and different concentrations of either tyrosine or 6-methyltetrahydropterin cofactor, a 2-fold increase in enzyme Vma, is demonstrable, with no change in the Km for either substrate or cofactor. In contrast, in the presence of cAMP and ATP/Mg2+, both an increase in Vma.and an enhanced affinity for pterin cofactor are demonstrable. In the latter circumstance, the 2-fold increase in Vmax can be attributed entirely to the action of cAMP-independent protein kinase.The addition of either EGTA or CaCl2 does not modify the effect seen in the presence of ATP, suggesting that the effect of ATP/ Mg2+ is not mediated by a Ca2+-dependent protein kinase. These data support the existence of a cAMP-independent striatal protein kinase that can catalyze the activation of TyrOHase.In striatum, as in peripheral adrenergic tissues, the enzyme tyrosine hydroxylase [TyrOHase; tyrosine monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1. 14.16.2] catalyzes the first and rate-limiting step in the biosynthesis of the neurotransmitter dopamine (1-4). cAMP and analogs of this cyclic nucleotide are able to increase the activity of the enzyme in crude tissue preparations in the presence of added ATP and Mg2+ (ATP/Mg2+) (5)(6)(7)(8)(9)(10)(11), and this activation is associated with either an increased affinitv of enzyme for cofactor (5,7,11,12) or a reduction of feedback inhibition by dopamine or norepinephrine (7, 13). Presumably, cAMP activates cAMP-dependent protein kinase, releasing free catalytic subunit which in turn activates TyrOHase. In recent studies (14-18) it has been shown that the free catalytic subunit of cAMP-dependent protein kinase activates TyrOHase by directly phosphorylating the enzyme.In many of the earlier studies on the activation of TyrOHase by protein kinase, crude tissue extracts were used, and the constituents of the system responsible for the activation of the enzyme in the presence of cAMP and ATP/Mg2+ were not rigorously defined. In a number of studies (7-10), activation of TyrOHase by ATP/Mg2+ alone has been reported, and it had been assumed that this activation was attributable to the presence of free catalytic subunit of cAMP-dependent protein kinase, thus accounting for the lack of an...

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Section: Methodssupporting

confidence: 94%

Evidence for the involvement of a cyclic AMP-independent protein kinase in the activation of soluble tyrosine hydroxylase from rat striatum.

Andrews¹,

Langan²,

Weiner³

1983

Proc. Natl. Acad. Sci. U.S.A.

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“…The administration of exogenous cofactor results in enhanced hydroxylation in rat striatum in vivo (7), in cultures of sympathetic neurons (8), in striatal synaptosomes (9), and in the isolated hypogastric nerve-vas deferens preparation (10,11). A second line of evidence is the increase in dopamine synthesis produced by cyclic AMP or stimulation of catecholaminergic terminals that apparently is the result of the increased affnity of TyrOase for the pterin cofactor (12)(13)(14)(15). Finally, induction ofrat hypothalamus TyrOase by reserpine administration failed to enhance tyrosine hydroxylation in synaptosomes prepared from this tissue (16) unless exogenous H4B was added to the incubation medium (17).…”

mentioning

confidence: 99%

Tetrahydrobiopterin increases in adrenal medulla and cortex: a factor in the regulation of tyrosine hydroxylase.

Abou‐Donia¹,

Viveros²

1981

Proc. Natl. Acad. Sci. U.S.A.

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Tetrahydrobiopterin, the cofactor for tyrosine hydroxylase and other monooxygenases, is present in tissues at apparent concentrations much less than those necessary to saturate the corresponding enzymes. Reserpine treatment or insulininduced hypoglycemia in rats produces a statistically significant increase in the tetrahydrobiopterin content of both the adrenal medulla and the cortex. Adrenal denervation and hypophysectomy selectively block the increases in cofactor level in medulla and cortex, respectively, while cycloheximide prevents the increase in both tissues. Reserpine did not increase cofactor levels in liver, kidney, or corpus striatum but decreased that of the pineal gland. These results suggest that tetrahydrobiopterin is under neural control in the medulla and hormonal control in the cortex and that increases in cofactor may result from induction ofenzyme(s) in the biosynthetic pathway. These results demonstrate regulation of tissue tetrahydrobiopterin and are consistent with the suggestion that cofactor levels participate in the regulation of tyrosine hydroxylase in the adrenal medulla and may have a function, as yet undetermined, in the adrenal cortex.L-erythro-5,6,7,8-tetrahydrobiopterin (H4B) is an essential cofactor for tyrosine 3-monooxygenase [TyrOase; tyrosine hydroxylase; L-tyrosine, tetrahydropteridine:oxygen oxido reductase (3-hydroxylating); EC 1.14.16.2] (1), the rate-limiting enzyme in the biosynthesis ofthe neurotransmitters dopamine, norepinephrine, and epinephrine (2). There is considerable evidence for the short-term regulation oftyrosine hydroxylation by a decrease in the Km of TyrOase for its cofactor, H4B (for recent reviews, see refs. 3 and 4). Delayed or long-term regulation of tyrosine hydroxylation and catecholamine synthesis is obtained by increased synthesis ofTyrOase, dopamine-,B-hydroxylase, and catecholamine storage vesicles (5, 6). Several lines of evidence suggest that H4B is present in concentrations substantially less than Km for TyrOase in monoaminergic neurons. The administration of exogenous cofactor results in enhanced hydroxylation in rat striatum in vivo (7), in cultures of sympathetic neurons (8), in striatal synaptosomes (9), and in the isolated hypogastric nerve-vas deferens preparation (10, 11). A second line of evidence is the increase in dopamine synthesis produced by cyclic AMP or stimulation of catecholaminergic terminals that apparently is the result of the increased affnity of TyrOase for the pterin cofactor (12-15). Finally, induction ofrat hypothalamus TyrOase by reserpine administration failed to enhance tyrosine hydroxylation in synaptosomes prepared from this tissue (16) unless exogenous H4B was added to the incubation medium (17). Although regulation of monoamine synthesis through changes in the availability of reduced biopterin has been proposed (18), there is no experimental evidence for physiological regulation of endogenous cofactor levels. The long-term regulation of catecholamine synthesis could create a paradoxical situation if t...

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“…4,[9][10][11][12] The marked increase in catecholamine levels using the decapitation method has been suspected to be due to the activation of adrenal tyrosine hydoxylase, the rate-limiting enzyme in the synthesis of catecholamines 22) and sympathoadrenal activation due to acute hemorrhage. 23,24) In contrast, it is thought that plasma DOPAC levels were less affected by decapitation, as the change in plasma DOPAC levels did not depend on adrenal tyrosine hydoxylase activity 4) and there was a time lag in the metabolism of DA to DOPAC.…”

Section: Discussionmentioning

confidence: 99%

Increases in Plasma Dihydroxyphenylacetic Acid Levels in Decapitated Mice after Exposure to Various Stresses.

Harikai

Fujii

Onodera

et al. 2002

Biological & Pharmaceutical Bulletin

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This study investigated changes in plasma levels of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) in decapitated mice in response to the variable stresses of restraint, restraint and water immersion, and foot shock. DOPAC levels, but not norepinephrine (NE) and epinephrine (EPI) levels, increased upon exposure to these stresses. Plasma DOPAC levels measured using the decapitation method in rats were then compared with those measured using the catheter method. The NE and EPI levels in plasma measured using the decapitation method were much higher than those using the catheter method under basal conditions. In contrast, differences in the levels of DOPAC in plasma were smaller than those of NE and EPI under basal conditions using in both methods; furthermore parallel changes in plasma DOPAC levels occurred during restraint and water immersion stresses. These results indicate that the plasma DOPAC levels measured in mice using the decapitation method were clearly increased by the different stresses. Furthermore, in rats there were correlations between the decapitation and catheter methods for plasma levels of DOPAC. Thus the change in plasma DOPAC levels measured using the decapitation method is a good indicator of stress responses involving sympathoneural activity.

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Tyrosine hydroxylase regulation in the central nervous system

Cited by 58 publications

References 140 publications

Evidence for the involvement of a cyclic AMP-independent protein kinase in the activation of soluble tyrosine hydroxylase from rat striatum.

Evidence for the involvement of a cyclic AMP-independent protein kinase in the activation of soluble tyrosine hydroxylase from rat striatum.

Tetrahydrobiopterin increases in adrenal medulla and cortex: a factor in the regulation of tyrosine hydroxylase.

Increases in Plasma Dihydroxyphenylacetic Acid Levels in Decapitated Mice after Exposure to Various Stresses.

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