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)

We report here the isolation of a cDNA clone containing the full coding region of bovine phenylethanolamine N-methyltransferase (PNMTase, EC 2.1.1.28, S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase). The complete nucleotide sequence of the cDNA has been determined, and the amino acid sequence of PNMTase deduced. Cultured cells transfected with an expression vector containing this cDNA produced high levels of PNMTase enzymatic activity. Antibodies specific for tyrosine hydroxylase [EC 1.14.16.2, tyrosine 3-monooxygenase; L-tyrosine, tetrahydrobiopterine: oxygen oxidoreductase (3-hydroxylating)], the first enzyme in the catecholamine pathway, possess a striking affinity for the PNMTase protein synthesized in vitro. Comparison of the deduced amino acid sequence of bovine PNMTase to rat tyrosine hydroxylase reveals that PNMTase shares significant homology with tyrosine hydroxylase and supports previous protein and immunological data suggesting that the catecholamine biosynthetic enzymes are structurally related.
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PMID:Complete nucleotide and deduced amino acid sequence of bovine phenylethanolamine N-methyltransferase: partial amino acid homology with rat tyrosine hydroxylase. 287 53

Using beta-bungarotoxin (beta-BTX) as a tool to eliminate the preganglionic cholinergic nerve supply to the embryonic rat adrenal gland, we have investigated whether or not these nerves affect the differentiation of embryonic chromaffin cells (pheochromoblasts). Rat fetuses received a single injection of 1 or 2 micrograms beta-BTX or an identical volume of saline at embryonic day (E) 17 and were taken for morphological and biochemical analyses at E 21. Administration of beta-BTX caused a 15 to 20% reduction in body weight, crown-rump-length and adrenal weight. Spinal cord development was reduced and acetylcholinesterase-positive cells in ventral and lateral columns were virtually absent in toxin-treated animals. In adrenal glands, a decrease of choline acetyltransferase activity to 13% of control levels and a concomitant decrease of ultrastructurally identifiable nerve fibers and axon terminals revealed that application of 2 micrograms beta-BTX effectively reduced the neuronal input to E 21 adrenal glands. Values for total adrenal catecholamines, relative amounts of adrenaline and noradrenaline, tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities were unaltered. All ultrastructural features of pheochromoblasts (except the lack of synapse-like axon terminals) were inconspicuous. Corticosterone levels in adrenals and plasma were identical to controls. These data strongly suggest that normal embryonic development of adrenal chromaffin cells does not require an intact nerve supply.
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PMID:Destruction of the preganglionic nerves by beta-bungarotoxin does not interfere with normal embryonic development of the rat adrenal medulla. 287 9

The activities of the catecholamine synthetic enzymes tyrosine hydroxylase and phenylethanolamine N-methyltransferase, and the concentrations of the catecholamines and their respective metabolites, have been measured in the dorsal and ventral halves of the brainstem at various ages in the embryonic and adult rat. The activity of phenylethanolamine N-methyltransferase in both parts of the brainstem at day 14 of gestation is at or greater than adult levels and thereafter displays relatively small variations during ontogeny. Tyrosine hydroxylase activity, in contrast, is undetectable at day 14 and increases slowly, achieving only 20-25% of adult values by day 18 of gestation. Adrenaline concentrations correlate well with the activity of phenylethanolamine N-methyltransferase, showing a precocious development, whereas noradrenaline and 3,4-dihydroxyphenylethylamine (dopamine) concentrations are more closely related to the enhancement of tyrosine hydroxylase activity; at day 18 of gestation, for example, they are only 5 and 10%, respectively, of the adult values. The concentrations of the metabolites of noradrenaline and dopamine are suggestive of a high rate of turnover. These results confirm previous immunocytochemical evidence of a tardy appearance of tyrosine hydroxylase-like immunoreactivity in the phenylethanolamine N-methyltransferase-positive perikarya of the embryonic medulla oblongata. In addition, the abundance of adrenaline in this area at early gestational stages strongly suggests that, despite the paucity of tyrosine hydroxylase, phenylethanolamine N-methyltransferase is active in vivo and is utilizing a substrate other than noradrenaline. It is likely, however, that at later stages of gestation, when tyrosine hydroxylase is present at sufficient activity to supply noradrenaline, the conventional synthetic pathway for adrenaline formation comes into being.
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PMID:Abundance in the embryonic brainstem of adrenaline during the absence of detectable tyrosine hydroxylase activity. 287 72

A monoclonal antibody against the rat liver glucocorticoid receptor was used in combination with rabbit antibodies against tyrosine hydroxylase, phenylethanolamine N-methyltransferase, and 5-hydroxytryptamine to demonstrate strong glucocorticoid receptor immunoreactivity in large numbers of central monoaminergic nerve cell bodies of the male rat. The receptor immunoreactivity was predominantly located in the nucleus, whereas the tyrosine hydroxylase, phenylethanolamine N-methyltransferase, and 5-hydroxytryptamine were detected mainly in the cytoplasm. The vast majority of the noradrenergic nerve cell bodies of groups A1-A7 and of the 5-hydroxytryptaminergic cell bodies of groups B1-B9 were found to contain strong glucocorticoid receptor immunoreactivity. The majority of the phenylethanolamine N-methyltransferase-immunoreactive nerve cells of the adrenergic cell groups C1-C3 and of the dorsal subnuclei of the nucleus tractus solitarius in the medulla oblongata were also strongly immunoreactive for glucocorticoid receptor. In the midbrain dopaminergic groups A8-A10, moderately (A8, A9) to strongly (A10) glucocorticoid receptor-immunoreactive cells were found, ranging from 40 to 75% of the total population. In the hypothalamic dopaminergic cell groups, all the cells of groups A12 and A14, as well as the majority of the dopaminergic cells of the zona incerta (A13), were found to contain moderate to strong glucocorticoid receptor immunoreactivity, but none of the large dopaminergic cells of the posterior hypothalamus (A11) showed such immunoreactivity.
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PMID:Glucocorticoid receptor immunoreactivity in monoaminergic neurons of rat brain. 287 85

Adrenal medullary function and myocardial adrenergic receptors were investigated in streptozotocin-treated diabetic rats. The animals were rendered diabetic by a single i.v. injection of streptozotocin (STZ, 65 mg/kg) and killed 60 days after treatment. Adrenal tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) activities were increased by 52, 28 and 39%, respectively, in the STZ diabetic rats. In addition, adrenal concentrations of dopamine (+52%) norepinephrine (+46%), and epinephrine (+33%) were elevated significantly (P less than 0.05). Increased adrenal TH activity reflected an increased Vmax, but no change in Km. Receptor densities (Bmax), determined by [3H]prazosin and [3H]dihydroalprenolol binding, were decreased by 24 and 25%, respectively, in the myocardium of 60-day diabetic rats. Insulin-induced chronic hypoglycemia in the STZ diabetic rats produced a marked increase in the adrenal TH concentration (Vmax, +65% or +225%, respectively), as compared to control or diabetic rats, without changes in the affinity (Km) for the substrate. These results suggest that the STZ diabetic rat has abnormalities of catecholaminergic function of the adrenal medulla and myocardial adrenergic receptors, which may contribute to the development and maintenance of many of the hemodynamic and metabolic defects described in this animal model of diabetes mellitus.
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PMID:Adrenal catecholamine metabolism and myocardial adrenergic receptors in streptozotocin diabetic rats. 288 57

The prenatal and postnatal development of the rat retroperitoneal paraganglia were studied using the formaldehyde-induced catecholamine fluorescence (FIF) method. In addition, the transmitter composition of the paraganglionic cells of the newborn rat was analyzed by immunohistochemical demonstration of the catecholamine-synthesizing enzymes. The first fluorescent preaortic cells were detected in the 13.5-day-old embryos. One day later these cells constituted a distinct organ with moderately fluorescent cells, and in 15.5-day-old embryos this organ consisted cranially of moderately fluorescent and caudally of brightly fluorescent cells. The organ reached its largest size at birth and afterwards fibrous material increased between the fluorescent cells. In 4-week-old animals, only small clusters of fluorescent cells were observed in the preaortic area although many small paraganglia were situated cranially near the coeliac ganglion. In the organ of the newborn rat, many cells showed bright FIF. In addition, some cells with only slight or moderate fluorescence as well as non-fluorescent cells were detected. The analysis of immunoreactivity to the catecholamine-synthesizing enzymes showed that there was a cell population with intense reactivity to both tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). These cells were considered as paraganglion-type cells. Some of them were also immunoreactive to phenylethanolamine N-methyltransferase (PNMT). In addition, there were cells with weak to moderate reactivity to TH and DBH but not to PNMT. Also totally negative cells were constantly seen. These findings were confirmed by using consecutive sections for the localization of different enzymes and by using the Tramu method to elute previous staining and by restaining the same sections with the other antibodies. It is concluded that the retroperitoneal paraganglia of newborn rat consist of many paraganglion-type cells containing noradrenaline, some of them containing also adrenaline, a few neuron-like cells with TH and DBH immunoreactivity, and cells containing no catecholamines.
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PMID:Pre- and postnatal development of rat retroperitoneal paraganglia. 288 7

The catecholamine-containing nerve fibers of the rat pituitary were studied by immunohistochemical demonstration of the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). Immunohistochemical demonstration of TH confirms earlier catecholamine fluorescence histochemical studies showing a fine network of varicose fibers in both the intermediate and the neural lobe, with the most dense aggregation of fibers at the border between the lobes. DBH-immunoreactive fibers were much less in number, and confined to the neural lobe, where both vascular and parenchymal fibers were seen. With the antibody to PNMT bright staining was seen in all the glandular cells of the intermediate lobe, while the neural lobe was negative. No immunoreactive structures were observed in the anterior lobe. Functionally the study confirms the presence of an extensive dopaminergic innervation of the neurointermediate lobe, giving an anatomical basis for the tonic inhibitory action of dopamine on the intermediate lobe cells and for recent observations attributing dopamine a local regulatory function also in the neural lobe. In addition to vascular noradrenaline-containing fibers as described earlier the study shows parenchymal DBH-immunoreactive fibers in the neural lobe, suggesting a local role for noradrenaline in this lobe. The nature of the cellular PNMT-immunoreactivity in the intermediate lobe remains to be established. The cellular localization of the PNMT-immunoreactivity was distinctly different than that of the alpha-MSH-immunoreactivity within the intermediate lobe cells and reserpine treatment did not affect the PNMT-immunoreactivity although it induced a heterogeneous depletion of alpha-MSH and related peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Catecholamine-synthesizing enzymes in the rat pituitary. An immunohistochemical study. 288

The effects of nerve growth factor (NGF) and ciliary neuronotrophic factor (CNTF) on catecholamine content and in vitro activities of tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) were studied in adrenal chromaffin cells cultured from 8-day-old rats. Both NGF and CNTF enhanced chromaffin cell survival and partially prevented losses of adrenaline during the 4-day culture period in a dose-dependent manner. CNTF was more potent, although cellular levels of adrenaline and noradrenaline were not maintained. NGF did not add to the effect of CNTF. The effect of CNTF on catecholamine storage was not accompanied by changes in the activities of TH and PNMT. In contrast, NGF induced TH but not PNMT activity. These data indicate differences between the mechanisms by which NGF and CNTF affect adrenal chromaffin cells.
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PMID:Differential effects of nerve growth factor and ciliary neuronotrophic factor on catecholamine storage and catecholamine synthesizing enzymes of cultured rat chromaffin cells. 288 75

We studied the organization of projections from the C1 adrenergic and A1 noradrenergic cell groups in the ventrolateral medulla (VLM) to the hypothalamus and the spinal cord by using a combination of retrograde transport of fluorescent tracers and immunocytochemistry. Three issues were addressed. Neurons in the VLM that stain immunohistochemically for phenylethanolamine N-methyltransferase (PNMT) have been assumed to be adrenergic. However, the presence of PNMT-immunoreactive neurons in the hypothalamus that do not stain for tyrosine hydroxylase (TH) prompted us to re-evaluate the VLM by an elution-restaining immunohistochemical procedure. We confirmed that nearly all of the rostral medullary PNMT-immunoreactive neurons also stained for TH. By contrast, in the caudal medulla, very few TH-positive neurons stained for PNMT. Neurons of the C1 group in the rostral VLM project both to the thoracic spinal cord and to the hypothalamus. To determine whether individual C1 neurons send collaterals to the hypothalamus and spinal cord, we injected different-colored fluorescent dyes (diamidino yellow or fast blue) into the thoracic spinal gray matter and either the median preoptic (MnPO) or paraventricular (PVH) nuclei of the hypothalamus. Very few double-labeled neurons were found in the VLM, indicating that hypothalamic and spinal cord projections arise from almost completely independent populations of cells. Approximately half of the neurons projecting to the spinal cord from rostral VLM were not immunoreactive for TH or PNMT, indicating that a substantial part of this projection is noncatecholaminergic. The MnPO and the PVH both receive extensive catecholaminergic inputs from the VLM. We also used fluorescent retrograde tracers to determine whether individual VLM neurons send collaterals to both hypothalamic sites. Approximately 20% of neurons projecting to the MnPO in the rostral two thirds of the VLM also sent collaterials to the PVH, nearly all of these neurons being TH-positive. The collateralization of the VLM catecholaminergic projection to the hypothalamus may provide an anatomical substrate for integration of fore-brain participation in cardiovascular regulation. In contrast, the adrenergic projection from the VLM to the intermediolateral column of the spinal cord arises from a separate population of neurons.
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PMID:Organization of central adrenergic pathways: I. Relationships of ventrolateral medullary projections to the hypothalamus and spinal cord. 288 48

Postnatal genesis of small, intensely fluorescent cells was studied in the rat superior cervical ganglion by combining immunocytochemistry of tyrosine hydroxylase with tritiated thymidine autoradiography. After injection of tritiated thymidine during the first postnatal week, silver grains were observed over the nuclei of many small cells with intense staining for tyrosine hydroxylase, suggesting that SIF cells are dividing postnatally. Cell counts in ganglia of rats sacrificed 2 h after tritiated thymidine showed that the rate of SIF cell proliferation was highest during the first postnatal week with approximately 20% of SIF cells dividing and that the rate declined thereafter. Counts of labeled SIF cells at 30 days in rats injected with tritiated thymidine on days 0, 2, 4, 6, 8, 10 or 14 revealed a peak of SIF cell birthdays on day 8. In these long-survival experiments, many labeled SIF cells were present in adult superior cervical ganglions. In contrast, only one labeled principal neuron was observed in a total of 450 sections. Glucocorticoid treatment of the rats during the first postnatal week paradoxically increased the number of SIF cells, but inhibited the rate of SIF cell proliferation. Dividing SIF cells immunoreactive for both tyrosine hydroxylase and phenylethanolamine N-methyltransferase were observed in glucocorticoid-treated rats. These observations suggest that many SIF cells are dividing during the first postnatal week. After cessation of division, these cells either remain SIF cells or die, but do not differentiate into principal neurons. Since glucocorticoids do not stimulate SIF cell proliferation, they must increase the number of SIF cells by biasing the differentiation of precursor cells in the superior cervical ganglion and/or enhancing SIF cell survival.
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PMID:Division of small intensely fluorescent cells in neonatal rat superior cervical ganglion is inhibited by glucocorticoids. 288 82


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