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)

By indirect immunohistochemistry, the present study examined the distribution of neuronal structures in the cat medulla oblongata, pons, and midbrain, showing immunoreactivity to aromatic L-amino acid decarboxylase (AADC), which catalyzes the conversion of L-3, 4-dihydroxyphenylalanine (L-DOPA) to dopamine, and 5-hydroxytryptophan to serotonin (5HT). With simultaneous and serial double immunostaining techniques, immunoreactivity to this enzyme was demonstrated in most of the catecholaminergic and serotonergic neurons. We could also demonstrate AADC-IR cell bodies that do not contain tyrosine hydroxylase (TH-) or 5HT-immunoreactivity (called "D-type cells") outside such monoaminergic cell systems. At the medullo-spinal junction, very small D-type cells were found within and beneath the ependymal layer of the 10th area of Rexed surrounding the central canal. D-type cells were localized in the caudal reticular formation, nucleus of the solitary tract, a dorsal aspect of the lateral parabrachial nucleus, and pretectal areas as have been reported in the rat. Furthermore, the present study describes, in the cat brainstem, new additional D-type cell groups that have not been reported in the rat. Dense or loose clusters of D-type cells were localized in the external edge of the laminar trigeminal nucleus, dorsal motor nucleus of the vagus, external cuneate nucleus, nucleus praepositus hypoglossi, central, pontine, and periaqueductal gray, superficial layer of the superior colliculus, and area medial to the retroflexus. D-type cells were loosely clustered in the lateral part of the central tegmental field dorsal to the substantia nigra, extending dorsally in the medial division of the posterior complex of the thalamus and medial side of the brachium of the inferior colliculus. They extended farther rostrodorsally along the medial side of the nucleus limitans and joined with the pretectal cell group. Almost all these cells were very small and ovoid to round with 1-2 short processes with the exception of dorsal motor vagal cells. AADC-IR axons were clearly identified in the vagal efferent nerves, longitudinal medullary pathway, dorsal tegmental bundle rostral to the locus coeruleus. Serotonergic axons were identified not only in the central tegmentum field and lateral side of the central superior nucleus, but also in the ventral surface of the medulla oblongata. We describe principal densely stained fiber plexuses in the cat brainstem. The findings of the present study provide a morphological basis for neurons that decarboxylate endogenous and exogenous L-DOPA, 5HTP, and other aromatic L-amino acids.
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PMID:Aromatic L-amino acid decarboxylase-immunohistochemistry in the cat lower brainstem and midbrain. 208 22

Norepinephrine metabolism was investigated in 6-wk-old male Swiss albino copper-deficient and copper-supplemented mice. Beginning 4 d after birth of pups, dams were fed a diet low in copper (Cu) (0.4 mg/kg) and offspring were weaned to this diet at 21 d of age. Half the dams and their respective offspring received Cu (20 micrograms/ml) in the drinking water (+Cu) and served as controls. Unsupplemented offspring (-Cu) had lower liver Cu levels, exhibited anemia, and had increased heart weights but normal body weights compared to +Cu mice. Urinary output of norepinephrine and dopamine was higher, whereas output of creatinine and epinephrine was not different in -Cu mice compared to +Cu mice. Both fractional and calculated turnover of norepinephrine following inhibition of tyrosine 3-monooxygenase by alpha-methyl-p-DL-tyrosine methyl ester (alpha-MT) was higher in hearts from -Cu mice than in those from +Cu mice. Hearts and spleens from -Cu mice appeared to have higher tyrosine 3-monooxygenase activity as judged by increasing rates of L-dihydroxyphenylalanine accumulation following injection of m-hydroxybenzylhydrazine (NSD-1015), an inhibitor of aromatic amino acid decarboxylase. Turnover rates of norepinephrine for cerebellum were not different between +Cu and -Cu mice. Loss of norepinephrine from adrenal glands of mice injected with alpha-MT was not observed in the 8-h period studied. The smaller norepinephrine pool observed in organs of -Cu mice may have resulted from lower synthesis due to limiting dopamine-beta-monooxygenase activity and to higher turnover.
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PMID:Copper-deficient mice have higher cardiac norepinephrine turnover. 230 15

The islet cells of the mammalian pancreas are comprised of four different endocrine cell types, each containing a specific hormone. Islet cells also contain two enzymes of the catecholamine biosynthetic pathway : tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). The cell lineage relationships of these different cell types have not been examined and it is not known whether, during development, they originate from the same or from different precursor populations. In this study we used immunocytochemical procedures to determine whether developing pancreatic cells express markers common to endocrine and exocrine cell types. We found that acinar cell precursors express AADC prior to the appearance of an exocrine marker and that the expression of AADC in acinar cells persists throughout embryogenesis to the first month of postnatal life. At this time, acinar cells do not contain AADC. We also found that exocrine cells containing AADC never express other islet-cell markers. These findings suggest that while acinar and islet cells both arise from precursor cells containing AADC, these progenitor cells do not express a combined endocrine-exocrine phenotype.
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PMID:Expression of cell type-specific markers during pancreatic development in the mouse: implications for pancreatic cell lineages. 244 38

Tyrosine is the precursor of catecholamines. Small doses of tyrosine produce tachycardia and hypertension while higher doses produce bradycardia and hypotension in anaesthetised rats. The mechanism of these effects has not been established. An increased synthesis and release of catecholamines has been suggested to be the mechanism. Various pretreatments were given to anaesthetised Wistar rats to study the influence of a blockade of L-tyrosine metabolism and thus a blockade of catecholamine synthesis, on these cardiovascular effects: valine, which inhibits tyrosine uptake into brain, alpha-methyl-p-tyrosine, which blocks the rate-limiting enzyme, tyrosine hydroxylase, carbidopa and benserazide, which both inhibit dopa decarboxylase, and desipramine, which blocks catecholamine re-uptake. Benserazide and alpha-methyl-p-tyrosine partially blocked the stimulatory effects of tyrosine. None of the pretreatments were able to block effectively the inhibitory effects of L-tyrosine. Therefore, the metabolism of tyrosine to form catecholamines may be involved in the stimulatory but not in the inhibitory cardiovascular effects of L-tyrosine. Valine pretreatment did not antagonize the depressant effects of tyrosine. Since valine blocks the uptake of L-tyrosine into the brain, the depressant effects of L-tyrosine might be peripheral rather than central in origin.
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PMID:Cardiovascular effects of L-tyrosine: influence of blockade of tyrosine metabolism. 256 1

The effects of thyroidectomy and thyroid hormone replacement on the mass and in situ molar activity of tyrosine hydroxylase (TH) in the median eminence (ME) and superior cervical ganglia (SCG) of male rats were investigated. The tissue specificity of these effects were evaluated by comparing the ME with the superior cervical ganglion (SCG). All animals were thyroparathyroidectomized (Tx) or sham Tx. Tx rats were treated daily for 3 weeks with 0.15 M NaCl (solvent vehicle) or L-thyroxine (T4). Two doses of T4, 10 and 100 micrograms/day/kg BW, were used. Sham Tx rats were treated with 0.15 M NaCl. All animals were studied on the day following the last treatment. The mass of TH was determined using an immunoblot assay, and the in situ activity of TH was calculated from the rate of intracellular accumulation of L-dihydroxyphenylalanine (DOPA) after administration of an inhibitor of DOPA decarboxylase activity. In the ME, thyro-parathyroidectomy resulted in a 40% increase in the mass and a 100% increase in the in situ molar activity of TH over that of sham Tx rats. Compared to Tx animals given 0.15 M NaCl, Tx rats treated with a low dose of T4 (10 micrograms/day/kg BW) had a reduced quantity of TH in the ME, but the molar activity of the enzyme was increased. Treatment of Tx rats with a high dose of T4 (100 micrograms/day/kg BW) restored TH mass but not the in situ activity of TH in the ME to the level seen in sham Tx rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mass and in situ molar activity of tyrosine hydroxylase in the median eminence. Effect of thyroidectomy and thyroid hormone replacement. 257 Mar 69

The concentration of 3,4-dihydroxyphenylalanine (DOPA) was low in the pancreas, liver, kidney, spleen, salivary glands, heart and adrenal glands of untreated mice, but increased following inhibition of DOPA decarboxylase by 3-hydroxybenzylhydrazine. The ratio of the accumulation of DOPA to the concentration of noradrenaline (i.e. the density of sympathetic nerves) was greater in the kidney, liver and, particularly, pancreas than in the other organs studied, suggesting that DOPA occurred outside sympathetic nerves in these organs. The tyrosine hydroxylase inhibitor alpha-methyltyrosine almost completely inhibited the accumulation of DOPA in all organs. The DOPA accumulation was enhanced in all organs by the alpha-adrenoceptor antagonists phentolamine and yohimbine. The results indicate that the DOPA was formed in the sympatho-adrenal system. In the pancreas, liver and kidney, most of the DOPA accumulated might have been formed outside these organs and transferred there via the bloodstream.
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PMID:Transfer of DOPA from the sympatho-adrenal system to the pancreas, liver and kidney via the blood circulation. 257 May 6

In order to clarify further the neural control of digestive tract function, we have compared the neuronal localization of tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC) in rat small intestine. Immunoreactivity for TH was found in numerous varicose axons associated with neurons of the enteric plexuses and in axons within the circular muscular coat and the mucosal villi. Axons with AADC immunoreactivity had a similar distribution, but were sparser in the enteric plexuses and musculature than those containing TH. Chronic extrinsic denervation of a segment of intestine removed all TH-positive nerves from that region. By contrast, the intensity of AADC immunoreactivity was enhanced and more AADC-positive axons were visible than in adjacent intact areas of intestine. The AADC-positive axons appear to represent the intrinsic 'amine-handling' neurons rather than intrinsic tryptaminergic neurons or extrinsic dopaminergic neurons, and the effect on AADC activity of removing the extrinsic nerve supply suggests that this normally exerts some restraining influence on the metabolism of the 'amine-handling' population.
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PMID:Extrinsic denervation elevates neuronal aromatic L-amino acid decarboxylase immunoreactivity in rat small intestine. 257 Jul 72

p-Chlorophenylalanine was administered to rats to inhibit hepatic phenylalanine hydroxylase activity. Two days later, phenylalanine injection was noted to produce substantial increases in serum phenylalanine levels, and relatively modest increments in serum tyrosine levels. Rats injected with p-chlorophenylalanine 2 days earlier showed a normal light-induced activation of retinal tyrosine hydroxylase activity in vivo, measured as dihydroxyphenylalanine accumulation following pharmacologic inhibition in vivo of aromatic L-amino acid decarboxylase activity. In addition, tyrosine injection into p-chlorophenylalanine-treated rats in the light produced anticipated increments in retinal tyrosine hydroxylation rate, showing the enzyme to be functionally normal. The acute administration of phenylalanine (62.5-500 mg/kg i.p.) to p-chlorophenylalanine-treated rats produced dose-related increments in retinal phenylalanine. In vivo tyrosine hydroxylation rate in retina was normal at all doses below 300 mg/kg. However, at the highest dose (500 mg/kg), when retinal phenylalanine levels were almost 5-times normal tyrosine hydroxylation rate consistently fell (to about half-normal values). These results demonstrate that very large elevations in tissue phenylalanine levels do not stimulate tyrosine hydroxylation in vivo, and that at extremely high levels phenylalanine inhibits tyrosine hydroxylation rate.
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PMID:In vivo tyrosine hydroxylation rate in retina: effects of phenylalanine and tyrosine administration in rats pretreated with p-chlorophenylalanine. 257

Immunohistochemical studies of monoamine neurons were performed to evaluate toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on young adult mice and compare them with those of their offspring. Mice, 9-11 weeks old (C57BL/6J), injected subcutaneously with a large dose of MPTP (17 mg/kg per day) during pregnancy on Day 9 and 12 of gestation (G9 and G12) miscarried and were examined at 13 weeks of age. Conversely, mice treated during pregnancy with sequential low dose of MPTP (2.8 mg/kg per day at G9-G17 for 8 days) successfully delivered their babies and were examined at the age of 15 weeks. Baby mice were examined at 1 and 6 weeks of age. The tyrosine hydroxylase-, aromatic L-amino acid decarboxylase- and dopamine (DA)-immunoreactive density of caudoputamen was reduced in 13-week-old mice treated with high dose of MPTP but not in the 15-week-old mothers exposed to a low dose of MPTP as compared to their respective controls. The DA-immunoreactive density of the caudoputamen was the only staining that was reduced in both 1- and 6-week-old baby mice. In conclusion, these results demonstrate that MPTP injected to pregnant mice causes a DA depletion in the striatum of their offspring indicating a transplacental effect of MPTP. The findings also indicate that fetal brain is more susceptible to MPTP toxicity than the brain of young pregnant mice.
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PMID:Transplacental effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on brain dopaminergic neurons in the mouse. An immunohistochemical study. 257 40

In the present study, we obtained genetically manipulated non-neuronal cells which synthesize a catecholamine precursor for future use in the intracerebral grafting. Human type 1 tyrosine hydroxylase (TH, EC 1. 14. 16. 2) cDNA was inserted into eukaryotic expression vector pKCRH2 and was co-transfected into C6 cells with plasmid pSV2neo. Expression of the TH minigene was screened by immunocytochemical staining with TH antibody and immunoblotting analysis. Several clones of the C6 transfectants that produce TH molecules were obtained. These cells showed TH activity and the product, L-DOPA, was detected intracellularly due to the absence of L-amino acid decarboxylase (AADC, EC 4. 1. 1. 28) activity. It was found that a large amount of L-DOPA was released from the cells into the culture medium. These transfectants were transplanted into rat brain and the expression of TH was examined immunohistochemically. At the 10th day following transplantation, a mass of C6 cells which was heavily stained with TH antibody was observed in the brain. These findings may provide us an opportunity to investigate the effects of intracerebral transplantation of non-neuronal cells that produce catecholamine or its precursor.
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PMID:[Current advances in neural transplantation]. 257 49


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