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

Long-term administration of high doses of xylitol and other polyols in rats has been associated with an increase in adrenal medullary hyperplasia and neoplasia. In order to exclude age-related factors and to differentiate between unspecific stress reactions and direct effects of the compound administered, a model was developed for quantifying early adrenomedullary responses. Male SD rats were fed xylitol (10% or 20% in the diet) for 2 and 8 weeks, and early biochemical changes were correlated with a stereological analysis of the adrenal medulla. At first, the in vivo rate of catecholamine (CA) biosynthesis was slightly decreased (at 2 weeks). This was followed by an increase in dopamine-beta-hydroxylase (DBH) activity (at 8 weeks). By that time, the total chromaffin cell volume had increased and the number of chromaffin cells per reference volume had decreased in a dose-dependent way. The total number of chromaffin cells per adrenal gland showed a distinct tendency towards an increase. Adrenal epinephrine and norepinephrine contents were not altered, and both tyrosine hydroxylase and phenylethanolamine-N-methyltransferase activities remained unchanged. These data suggest that continued xylitol administration evoked an inhibitory effect on CA synthesis that, together with stimulation of the adrenal medulla brought about by the compound, resulted in compensatory medullary hypertrophy and hyperplasia.
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PMID:Early biochemical and morphological changes of the rat adrenal medulla induced by xylitol. 401 95

The development of a sensitive and specific enzymatic assay for dopamine-beta-hydroxylase has enabled us to measure the activity of this enzyme in several tissues where it has previously been measured. The administration of reserpine leads to an increase in dopamine-beta-hydroxylase activity in the rat adrenal, heart, salivary gland, and in sympathetic ganglia. The increase in the heart is preceded by a small but significant fall. We have confirmed the increase in tyrosine hydroxylase which follows the administration of reserpine and have found that the activity of phenylethanolamine-N-methyltransferase also increases after administration of this drug. The activities of two enzymes not involved in the synthesis of catecholamines, monoamine oxidase and lactate dehydrogenase, are not affected by reserpine treatment. The rise of dopamine-beta-hydroxylase activity in the sympathetic ganglia is blocked by surgical decentralization.
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PMID:Neurally mediated increase in dopamine-beta-hydroxylase activity. 431 16

The distribution of catecholaminergic fibers and cell bodies in the paraventricular and supraoptic nuclei of the hypothalamus was investigated with immunohistochemical methods in the adult albino rat. Sections through the nuclei were stained with antisera to the catecholamine synthesizing enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT). The results suggest that adrenergic (PNMT-stained) fibers innervate the entire parvocellular division of the paraventricular nucleus, although the highest density of fibers was found in the medial part of the division. Only widely scattered adrenergic fibers are found in the magnocellular division of the nucleus and in the supraoptic nucleus. Noradrenergic fibers appear to innervate the periventricular zone of the paraventricular nucleus and those parts of the paraventricular and supraoptic nuclei that contain predominantly vasopressinergic neurons in both the normal and in the homozygous Brattleboro rat. Significant numbers--somewhat more than 500--of dopaminergic (TH-stained) neurons are found in the paraventricular nucleus; the cells are distributed throughout the nucleus but are concentrated in the medial and periventricular parts of the parvocellular division. Double-labeling experiments with the retrogradely transported tracer true blue indicate that between 4% and 8% of the dopaminergic neurons in the paraventricular nucleus project to the region of the dorsal vagal complex and/or thoracic levels of the spinal cord. It is concluded that adrenergic inputs to the paraventricular nucleus may influence cells that project to the median eminence and to preganglionic autonomic cell groups in the medulla and spinal cord. Noradrenergic inputs to the supraoptic and paraventricular nuclei may influence primarily vasopressinergic cells that project to the posterior lobe of the pituitary, as well as cells in the periventricular part of the paraventricular nucleus that project to the median eminence.
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PMID:An immunohistochemical study of the organization of catecholaminergic cells and terminal fields in the paraventricular and supraoptic nuclei of the hypothalamus. 611 72

Catecholamine (CA) metabolism in peripheral organs of lean and obese, 3-4 and 7-8 month (mo) old male Zucker rats was studied to define further the known abnormalities of peripheral sympatho-adrenal functions in the obese rat. Norepinephrine (NE) levels in all sympathetically innervated organs from obese rats (aorta, heart, pancreas, brown adipose tissue and white adipose tissue) were decreased to 9-55% of those in lean rats at 3-4 mo. NE turnover, measured by inhibition of tyrosine hydroxylase (TH) with a-methyl-p-tyrosine, was also decreased in these same organs. NE levels and turnover were also decreased (by 50-95%) in many, but not all organs assayed of 7-8 mo old obese rats, while there were inconsistent changes in organ dopamine and epinephrine levels at both ages. Decreased NE metabolism was associated with decreased dopamine-beta-hydroxylase (D beta H) activity in every organ assayed from obese rats at 3-4 mo and 7-8 mo of age except in the superior cervical ganglia of 7-8 mo old rats. There were no consistent changes in TH or phenylethanolamine-N-methyltransferase activities. In 3-4 mo old obese rats, decreased D beta H activity was associated with decreased immunoprecipitable enzyme protein in the hearts but not in the adrenal glands, where differences in the affinity for substrate appeared to explain the activity differences. These results suggest that the previously reported defect in stress-induced plasma NE levels in obese rats could be explained by decreased D beta H activity in nerve terminals of their sympathetic nervous system and that, in this case, D beta H may play an important role in the regulation of NE synthesis.
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PMID:Defective catecholamine metabolism in peripheral organs of genetically obese Zucker rats. 611 28

The initial appearance and development of noradrenergic and adrenergic phenotypic characters was studied in the rat embryo by immunocytochemical methods. Tyrosine hydroxylase and dopamine-beta-hydroxylase (noradrenergic enzymes) appeared at 11.5 days of gestation (Day E 11.5; 27-30 somites) in sympathetic ganglion primordia and in cells of the gut. While tyrosine hydroxylase and dopamine beta-hydroxylase immunoreactivity increased progressively in ganglion primordia, the enzymes disappeared in the gut cells after E 13.5. However, the gut cells themselves persisted, as indicated by the high-affinity uptake of noradrenaline (norepinephrine). Consequently, initial appearance of noradrenergic characters does not ensure persistence and subsequent development, indicating that early phenotypic expression is a mutable process. This contention was supported by the observations that pharmacological stress of pregnant rats in the form of reserpine, or treatment with glucocorticoids, prolonged the appearance of catecholamines in the gut cells. Thus, maternal-embryonic relations in general, and maternal glucocorticoids in particular, may influence embryonic phenotypic expression. Treatment of embryos with nerve growth factor also prolonged the appearance of noradrenergic characters in the gut cells. Expression of the adrenergic phenotype was apparently regulated differently from noradrenergic expression, since phenylethanolamine-N-methyltransferase (PNMT), the adrenaline-(epinephrine)-synthesizing enzyme, was undetectable in ganglion primordia and gut cells. PNMT initially appeared at E 17.5 in cells which had migrated to be adrenal anlage. Extensive studies suggest that the initial appearance of PNMT occurs independently of glucocorticoid regulation, while subsequent development is dependent on corticoids.
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PMID:Transmitter phenotypic expression in the embryo. 611 22

1. We sought to determine if catecholamine biosynthetic enzymes of spontaneously hypertensive rats (SHR) differed from those of normotensive Wistar--Kyoto (WKY) and Sprague--Dawley (SD) control rats before birth. 2. By immunocytochemical and biochemical methods we compared strains for the time of appearance and maturation of the enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT) in sympathetic ganglia and adrenals. 3. The time of appearance of enzymes was identical in all three strains: TH and DBH first appeared in sympathetic ganglia on embryonic day 11 (E11) and in adrenal medulla on E16. PNMT, restricted to adrenal medulla, appeared later on E18. 4. The activity of adrenal TH prenatally on E18 and E21 and at day of birth (P1) in SHR was approximately two fold that in WKY or SD rats. In contrast PNMT was lower in SHR but only on E18. 5. Thus, although the timing of the first expression of adrenergic phenotypes is similar in SHR and normotensive controls, the differences in TH activity in adrenals suggest an enhanced biosynthetic capacity for catecholamines in this strain before birth. 6. We conclude that SHR differ from normotensive rats from the first expression of some of the genes controlling catecholamine biosynthesis.
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PMID:Differences in utero in activities of catecholamine biosynthetic enzymes in adrenals of spontaneously hypertensive rats. 611 79

The activities of the three major catecholamine-synthesizing enzymes were determined in brain tissue pellets dissected from 500-micrometers thick horizontal sections of rat lower brainstem. The rostrocaudal distributions of the three enzymatic activities were generally not parallel, suggesting differences in the respective localization of the noradrenergic and adrenergic neurons. The difference was most important in the A2-C2 region where the maximal activity of phenylethanolamine-N-methyltransferase (EC 2.1.1.28) was located 1.5 mm more rostrally than the maximal activities of the tyrosine hydroxylase (EC 1.14.16.2) and dopamine beta-hydroxylase (EC1.14.17.1). This result indicates that a more specific dissection of the adrenergic and noradrenergic neurons could be performed in the A2-C2 area of the rat brainstem.
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PMID:Comparative microdistribution of the activity of catecholamine-synthesizing enzymes in horizontal sections of the rat lower brainstem. 612 60

A population of cells containing the enzymes tyrosine hydroxylase (TH) and dopa-decarboxylase (L-AADC) but not dopamine-B-hydroxylase (DBH) nor phenylethanolamine-N-methyltransferase (PNMT) can be detected with immunocytochemical techniques in the pancreas of mouse embryos at the 11th day of development (E 11). The presence of TH in embryonal pancreas is transient: TH is not observed after E 15. By use of a method for simultaneously detecting two antigens in the same section both TH and glucagon were visualized in the same cell on E 12. Double labelled cells comprised 10% of all stained cells. At E 14.5, some of the cells stained for TH also contained insulin. However, at the time somatostatin appeared no embryonal cells containing TH remained. We conclude that two cell types of the APUD series, i.e., the glucagon and insulin cells of pancreas, arise from transformation, in situ, of cells that transiently express a dopaminergic phenotype. These results suggest that peptide-containing cells in skin, brain and gut are linked by a common embryonic origin. They also raise the prospect that other peptidergic cells of the APUD series may have aminergic precursors.
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PMID:Linkage of the brain-skin-gut axis: islet cells originate from dopaminergic precursors. 612 86

1. Anatomic and biochemical indices of adrenal medullary function were studied in mice (Mus musculus) with hereditary mellitus (C57BL/KsJ, db/db). 2. In the diabetic mice increases in medullary catecholamine content and in the activities of tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenylethanolamine-N-methyltransferase were accompanied by increases in adrenal weight and size. 3. Morphometric study of adrenals from diabetic mice showed that the medulla was increased in size but had a lower cell density indicating that medullary hypertrophy as well as hyperplasia were probably responsible for this size increase. 4. These observations are consistent with the occurrence of chronic adrenal medullary stimulation in the diabetic syndrome of these mice.
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PMID:The adrenal medulla of the diabetic mouse (C57BL/KsJ, db/db): biochemical and morphological changes. 612 1

Newborn rats were daily injected with 0.2 mg hydrocortisone acetate for seven days. They were killed 1, 7 or 21 days after the last injection, together with untreated controls. Hydrocortisone caused a great increase in the number of the small, intensely fluorescent (SIF) cells and the appearance of similar small cells with intense immunohistochemical reactions for tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine (noradrenaline) N-methyltransferase (PNMT) in the superior cervical ganglion. At the same time, the adrenaline content and the PNMT activity of the ganglion greatly increased, while no significant changes were observed in the dopamine or noradrenaline content or TH or DBH activity. All these changes essentially disappeared after a recovery period of seven or 21 days. It is concluded that hydrocortisone caused a temporary increase in the number of SIF cells by causing a synthesis of TH, DBH and PNMT in previously existing small, non-fluorescent cells, which start to synthesize and store adrenaline, thus becoming intensely fluorescent SIF cells. These SIF cells are different from the normal SIF cells of the same ganglion, most of which appear at a later stage of postnatal development when response to hydrocortisone is lost, which contain TH but neither DBH nor PNMT, and which permanently remain in the ganglion.
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PMID:Effect of hydrocortisone on catecholamines and the enzymes synthesizing them in the developing sympathetic ganglion. 612 66


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