Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

According to the dopamine (DA) hypothesis of schizophrenia, there is a functional excess of dopaminergic activity within unspecified areas of the brain in schizophrenic patients. As a clinical test of this hypothesis, we administered metyrosine for three weeks to symptomatic chronic male schizophrenic patients who were maintained on suboptimal doses of neuroleptic agents. Metyrosine inhibits tyrosine hydroxylase, the rate-limiting enzymatic step in the synthesis of DA. No clinical improvement was observed, using the National Institute of Mental Health Inpatient Behavioral Rating Scale or the Brief Psychiatric Rating Scale. Central inhibition of DA synthesis by metyrosine was suggested, however, by (1) the development of extrapyramidal side effects and (2) a significant increase in plasma prolactin concentrations. Plasma chlorpromazine concentrations remained unchanged during metyrosine treatment. There was, nevertheless, a significant improvement on the scores of the Wechsler Adult Intelligence Scale Comprehension subtest, which measures judgment and common sense. This finding suggests that DA may be involved in the regulation of subtle psychological processes. The results are discussed in light of the DA hypothesis of schizophrenia and previous reports suggesting that metyrosine potentiates the antipsychotic effect of neuroleptics in schizophrenia.
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PMID:Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine. 1 74

A 12-year-old boy with a norepinephrine-secreting pheochromocytoma that caused hypertension resistant to oral alpha adrenergic blockade is reported. Resistance to alpha adrenergic blocking agents developed when the patient's daily propranolol dosage was lowered from 10 to 1 mg/kg. Subsequently, alpha methyl tyrosine, an inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, controlled the patient's blood pressure and was associated with reduction in total urinary catecholamine excretion. Norepinephrine content of the tumor and uninvolved adrenal gland removal at surgery was reduced. These findings confirm that alpha methyl tyrosine inhibited in vivo synthesis of catecholamines.
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PMID:Childhood pheochromocytoma: treatment with alpha methyl tyrosine for resistant hypertension. 1 59

The short- and long-term effects of neuroleptic drugs differ both clinically and biochemically. Short-term treatment with such a drug causes a kinetic activation of striatal tyrosine hydroxylase. Long-term treatment causes a prompt activation of the enzyme which is followed by a delayed, compensatory deactivation below control levels. Tolerance also develops to the stimulating effect of haloperidol on striatal dopamine turnover.
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PMID:Haloperidol: effect of long-term treatment on rat striatal dopamine synthesis and turnover. 1 17

Norepinephrine turnover rates and tyrosine hydroxylase activities were determined in the interscapular brown fat pad of the rat during cold acclimation, hyperthyroxinism, and after thyroidectomy. Rats were cold acclimated by placement in a cold room, one rat to a cage, for a period of 6 wk. Hyperthyroxinism was induced by daily subcutaneous injections of L-thyroxine (1 mg/kg) for 6 days. Norepinephrine turnover rate and enzyme activity were determined at the end of each experimental period and at 8 wk after thyroidectomy. The rate of norepinephrine turnover increased during cold acclimation and hyperthyroxinism and decreased after thyroidectomy. Cold acclimation resulted in a significant increase in tyrosine hydroxylase activity, whereas no significant effect on enzyme activity was observed in hyperthyroxinism or after thyroidectomy. None of the conditions produced a change compared to controls in the apparent Km of tyrosine hydroxylase for L-tyrosine. Cold acclimation resulted in a significant decrease in the apparent Km of tyrosine hydroxylase for pterin cofactor, whereas thyroxine treatment and thyroidectomy had no effect.
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PMID:Thyroid cold acclimation influences on norepinephrine metabolism in brown fat. 1 13

The effect of electrical stimulation on the membrane-bound tyrosine hydroxylasectivity of the rat hypothalamus synaptosomes was studied. The electrical stimulation caused an elevation of O2 consumption and the elevation of glycolysis indicating synaptosome excitation. The membrane-bound tyrosine hydroxylase activity increased under these conditions. The KM value for tyrosine decreased from 0.091 to 0.026 mM. Noradrenaline inhibition of the enzymatic activity diminished. It is assumed that the effect of depolarization on the catecholamine synthesis velocity in the nerve endings involves tyrosine hydroxylase modification.
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PMID:[Tyrosine hydroxylase activation upon electric stimulation of isolated hypothalamic nerve endings in rats]. 1 34

1. The development of nicotinic responses in the rat adrenal medulla was examined at various ages from 1 to 50 days of age by testing the ability of nicotine (10 mg/kg, s.c.) to deplete catecholamines and induce tyrosine hydroxylase. 2. Catecholamines were depleted 25% 3 h after injection of nicotine at all ages tested, but the degree of tyrosine hydroxylase induction 24 h after nicotine increased with age. 3. These data indicate that functional nicotinic receptors are present in the neonatal adrenal medulla before the development of functional splanchnic innervation, but that the development of the ability to induce tyrosine hydroxylase is not coupled directly to the development of secretory mechanisms. 4. The long-term effects of a single dose of nicotine (10 mg/kg, s.c.) administered to one day old rats were also examined. 5. After the short-term catecholamine depletion caused by nicotine, there were persistent elevations of catecholamines and tyrosine hydroxylase until 23 days of age; however, dopamine beta-hydroxylase remained elevated into young adulthood. 6. These data indicate that neonatal nicotine administration can produce long-term changes in adrenal catecholamine biosynthetic enzymes.
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PMID:Development of nicotinic responses in the rat adrenal medulla and long-term effects of neonatal nicotine administration. 1 46

The monodeiodination of T4 in rat liver homogenate was studied. The two possible products of this reaction show very different properties. The metabolically very active T3 is rather stable in this system whereas the biological inactive reverse T3 (rT3) disappears very rapidly. This explains the low apparent rT3 production in the incubation mixture even under optimal conditions and the peculiar pH profile. The T4 to T3 converting reaction can be increased by the addition of mercaptoethanol to the medium; no further activation is possible by several cofactors tested. The apparent KM of the reaction is 1.6 x 10(-6) M. Reverse T3 does inhibit the reaction non competitive; Ki = 2 x 10 (10-8) M. Alpha-methyl-para-tyrosine, a specific inhibitor of tyrosine hydroxylase, has no significant effect on the reaction.
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PMID:Properties of the thyroxine (T4) monodeiodinating system in rat liver homogenate. 1 99

The activities of monoamine biosynthetic enzymes were measured in brain regions of several hypertensive rat models at various ages. The types of hypertensive rats were the spontaneously hypertensive rat (SHR) and a stroke-prone substrain of the SHR as well as DOCA-salt and renal hypertensive rats. The genetically hypertensive rats had significantly elevated blood pressures as compared to the Wistar-Kyoto control rat after 5 weeks of age. During the early development of hypertension in the SHR, the activities of tyrosine hydroxylase in the hypothalamus and corpus striatum and of dopamine-beta-hydroxylase in the hypothalamus and pons-medulla were significantly higher than in the control rats. Tryptophan-hydroxylase was also elevated in the hypothalamus in SHR. From 3 to 8 weeks of age there appeared to be a significant correlation between hypothalamic dopamine-beta-hydroxylase activity and blood pressure in the hypertensive rats. In contrast, the activities of tyrosine hydroxylase and dopamine-beta-hydroxylase were slightly decreased in the DOCA-salt and renal hypertensive rats. It is suggested that noradrenergic or adrenergic neurons in the hypothalamus may participate in the initiation of elevated blood pressure in the genetic, but not in the DOCA-salt or renal hypertensive rats.
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PMID:Regional changes in the activities of aminergic biosynthetic enzymes in the brains of hypertensive rats. 1 54

Clinical reports indicate that cessation of treatment with the antihypertensive agent clonidine is associated with a withdrawal syndrome which may include a hypertensive overshoot of critical proportions. We have attempted to produce an animal model of this syndrome in rats. Rats were treated with clonidine in the drinking water (5 microgram/ml; total dose 300-500 microgram/kg/day) which produced a significant (approx. 20%) decrease in heart rate and blood pressure. Within 24 h of cessation of treatment a significantly greater (approximately 100 beats/min) heart rate was seen in treated animals than in control animals when measurements were made in conscious animals. No hypertensive overshoot was observed. Cessation of treatment was associated with an increase in sympatho-adrenal tone as shown by a trans-synaptic induction of adrenal tyrosine hydroxylase activity. Adrenal denervation prevented the rise in adrenal tyrosine hydroxylase seen after cessation of treatment. Administration of clonidine to pregnant rats (10th day until term) did not alter the development of adrenal tyrosine hydroxylase in the offspring. The data indicate that a withdrawal syndrome is produced upon cessation of chronic clonidine treatment.
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PMID:Withdrawal syndrome upon cessation of chronic clonidine treatment in rats. 1 57

Tyrosine hydroxylase is synthesized de novo in rat superior cervical ganglia in organ culture. The differential rate of synthesis is not increased significantly by the addition of nerve growth factor to the culture. Prior administration of nerve growth factor in vivo, however, leads to an augmented synthesis of tyrosine hydroxylase in ganglia subsequently cultured in vitro. The differential rate of tyrosine hydroxylase synthesis was increased by a factor of between 3 and 4. Increases in the differential rate of synthesis were detected within 6 h; the rate reached a maximum 24 to 36 h after a single injection of nerve growth factor. Administration of actinomycin D or of nerve growth factor antibody in vivo prevented the nerve growth factor-induced increase in the differential rate of tyrosine hydroxylase synthesis in vitro. However, the increase in the synthetic rate of tyrosine hydroxylase was not prevented by the addition of actinomycin D to the culture.
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PMID:Selective de novo synthesis of tyrosine hydroxylase in organ cultures of rat superior cervical ganglia after in vivo administration of nerve growth factor. 1 75


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