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At least 1,207 records · Page 67Linked to original sources
PubMed1992

Differential time course activation of the brain stem catecholaminergic groups following chronic adrenalectomy.

The activity of the brain stem catecholaminergic (CA) cell groups of the ventrolateral (A1C1) and dorsomedial (A2C2) medulla that are known to contain primarily nonadrenergic neurones (A1 and A2) and a smaller proportion of adrenergic cells (C1 and C2) as well as the noradrenergic group locus ceruleus (LC) in the dorsal pons was determined at various times up to 16 days following surgical adrenalectomy. The activity of the CA cell groups was estimated by the rate of tyrosine hydroxylation in vivo that was assessed by measuring the 3.4-dihydroxyphenylalanine (DOPA) accumulated 20 min following administration of DOPA decarboxylase inhibitor NSD 1015. In the medullary nuclei noradrenaline content was found around 40- up to 70-fold the adrenaline content. This result was taken as evidence that the noradrenergic cells are likely to provide the main contribution to the tyrosine hydroxylation rate that we measured. Endogenous DOPA content represented between 2 and 10% of the noradrenaline content. NSD 1015 induced an accumulation of DOPA that was linear for at least 20 min and reached at this time more than 10-fold the endogenous level. While no modification of the in vivo tyrosine hydroxylation rate was observed in the LC, a significant increase was found in both medullary groups following adrenalectomy. In the A1C1 group it was detected 8 days after surgery and was then maintained with a maximum that represented up to a 60% increase over the basal value. In the A2C2 group the activation was slightly delayed and less marked. Increase in ACTH level occurred much earlier: it was about 70% of the maximal level already 4 days following adrenalectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1986

A simplified 14CO2-trapping microassay for tyrosine hydroxylase activity.

This 14CO2-trapping microassay for tyrosine hydroxylase activity uses microtest tubes (1.5 or 2.0 ml) with pierceable caps for injecting the reaction mixture. A folded filter paper strip (1 X 4 cm) impregnated with Protosol is placed directly inside the top of the tube prior to capping in order to trap liberated 14CO2. The effects of several variables and components involved in the assay have been systematically studied. The tyrosine hydroxylation reaction may be optimized by incubating 300 micrograms protein with 150 microM L-Tyr, 0.8 mM 6MPH4, 1 mM FeSO4, and 0.12 M Tris-acetate buffer (pH 5.8) for 10 min at 37 degrees C. The DOPA decarboxylation reaction may be optimized by continual incubation of the tyrosine hydroxylation medium with 175 micrograms hog kidney aromatic-L-amino acid decarboxylase, 6.25 mM 3-iodotyrosine, and 0.125 M potassium phosphate buffer (pH 8.0) for 30 min at 37 degrees C. Under these conditions, the radioactivity of 14CO2 recovered after 1 h at 37 degrees C may reach 14,000 dpm, whereas the blank only has 300 dpm (less than 3% of test value). This microassay is fast (less than 2 h to complete all reactions) and convenient for performing a large number of determinations.

Animals↗
PubMed1977

Striatal lesions with kainic acid: neurochemical characteristics.

Stereotaxic injection of 2.5 microng of kainic acid, a rigid analogue of glutamate into the rat striatum caused a 70% reduction in the striatum of the cholinergic parameters, choline acetyltransferase, acetylcholine and synaptosomal uptake of choline and a similar reduction in the GABAergic parameters, glutamic acid decarboxylase, psi-aminobutyric acid (GABA) and synaptosomal uptake of GABA. In contrast, the striatal content of dopamine and the synaptosomal uptake of dopamine were unchanged, and the activity of tyrosine hydroxylase was significantly increased. Significant changes in the activity of neurotransmitter synthesizing enzymes were demonstrable within 6h after injection of 2.5 microng of kainic acid and maximal effects occurred at 48h; the activities of choline acetyltransferase and glutamic acid decarboxylase remained depressed up to 21 days after injection. The kinetic characteristics of striatal tyrosine hydroxylase were altered 48h after injection with a two-fold increase in the Vmax for tyrosine and a three-fold reduction in Km for the pteridine cofactor. In contrast to the effects of kainic acid, the injection of copper sulfate, a non-specific toxin, caused a proportionate reduction in the dopaminergic as well as the cholinergic and GABAergic presynaptic markers. The kainate lesion caused an 85% decrement in the activity of dopamine-sensitive adenylate cyclase, a 40% reduction in the specific binding of [3H]quinuclidinyl benzilate and a 195% increase in the specific binding of [3H]GABA in the striatum. The morphology of the kainate injected striatum was markedly altered with nearly a complete loss of intrinsic neurons, increased number of glial cells but intact internal capsule fibers. Intracerebral injection of nanomolar quantities of kainic acid appears to cause degeneration of neurons with cell bodies near the injection site while sparing axons terminating in or passing through the region.

Adenylyl Cyclases↗
PubMed1982

Bromocriptine-induced changes in dopamine and gamma aminobutyric acid in haloperidol withdrawn rats.

1. Daily administration of haloperidol (2 mg/kg, i.p.) for 35 days significantly decreased tyrosine hydroxylase activity as well as homovanillic acid in the corpus striatum of rats. 2. Long-term treatment with haloperidol significantly elevated (17%) glutamic acid decarboxylase activity as well as gamma-aminobutyric acid level in the corpus striatum. 3. Withdrawal of rats for 3 and 5 days after 32 and 30 days of haloperidol treatment increased the locomotor activity to 279% and to 211%, respectively, of control values. While haloperidol withdrawal decreased tyrosine hydroxylase activity, it produced no further change in glutamic acid decarboxylase activity and gamma-aminobutyric acid. 4. Daily injection of bromocriptine (2 mg/kg, i.p.) for 5 days in haloperidol-withdrawn rats decreased locomotor activity and dopamine release as evidenced by increased endogenous levels of dopamine and decreased homovanillic acid in striatum of rats. No further increase in striatal glutamic acid decarboxylase activity and GABA levels were reported after bromocriptine treatment. 5. Our data suggest that bromocriptine may elicit its beneficial effect in tardive dyskinesia patients by modifying dopamine turnover in the striatum.

Animals↗
PubMed1993

Simultaneous determination of in vivo hydroxylation of tyrosine and tryptophan in rat striatum by microdialysis-HPLC: relationship between dopamine and serotonin biosynthesis.

Using a microdialysis technique, the rat striatum was perfused with NSD-1015, an inhibitor of aromatic L-amino acid decarboxylase, and the amount of L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP) accumulating in dialysate was measured as an index of in vivo activities of tyrosine hydroxylase and tryptophan hydroxylase. NSD-1015 increased the concentration of L-DOPA much higher than that of 5-HTP in a dose-related manner (1-100 mumol/L). In order to examine the relationship between dopaminergic and serotonergic neurons in the striatum, either 5-HTP or L-DOPA was injected intraperitoneally to rats pretreated with benserazide, an inhibitor of peripheral decarboxylase. 5-HTP administration increased 5-HTP, but decreased L-DOPA in a dose-dependent manner. Conversely, 5-HTP concentration decreased in an association with the increased content of L-DOPA following L-DOPA administration. The decrease of 5-HTP caused by L-DOPA administration was not as remarkable as that of L-DOPA by 5-HTP injection. These results suggest that L-DOPA and 5-HTP, the precursor amino acids for catecholamines and indoleamines, could affect mutually each other neuronal activity through the inhibition of their rate-limiting enzymes.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

The distribution of neurotransmitters and neurotransmitter-related enzymes in the dorsomedial telencephalon of the pigeon (Columba livia).

Immunoreactivity to four neurotransmitters/transmitter-related enzymes was found in the dorsomedial telencephalon (hippocampal region) of the pigeon. Putative afferent fibers containing choline acetyltransferase-like, serotonin-like, and tyrosine hydroxylase-like immunoreactivity were seen in a fiber tract passing through the septo-hippocampal junction and along the medial wall of the hippocampal region. The most intensive labeling of neuropil and terminals of all four substances was found in the dorsomedial area of the hippocampal region. Glutamic acid decarboxylase-like immunoreactivity was seen in sparsely scattered cells throughout the region. These results are discussed in relation to hypotheses about the boundaries and subdivisions of the hippocampal region of the pigeon.

Afferent Pathways↗
PubMed1978

Neurotensin and its amide analogue [Gln4]-neurotensin: effects on brain monoamine turnover.

Intracerebroventricularly administered neurotensin and [Gln4]-neurotensin (50-200 microgram) increased the formation of Dopa in different brain regions of rats after inhibition of the aromatic L-amino acid decarboxylase. For both neuropeptides these increases were dose dependent (20-150%). In the corpus striatum [Gln4]-neurotensin was twice as active as neurotensin and it tended to be more active also in other brain regions. The brain tyrosine concentrations were also increased. [Gln4]-neurotensin (100-200 microgram) following inhibition of the aromatic L-amino acid decarboxylase, increased the accumulation of 5-hydroxytryptophan in all brain regions by 30-60%. In contrast, neurotensin was completely inactive. In both cases the brain tryptophan concentrations were increased. Both neurotensin and [Gln4]-neurotensin also accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine after inhibition of monoamine synthesis. These results show an increased brain monoamine turnover induced by both neuropeptides.

Animals↗
PubMed1991

Two patterns of dopa decarboxylase immunoreactivity in sympathetic axons supplying rat renal cortex.

Three ultrastructural cytochemical methods have been used to classify the innervation of the rat renal cortex. Every axon seen contained chromaffin-reactive, dense core vesicles and stained for tyrosine hydroxylase, indicating that they were all catecholaminergic. About 10% of the axons associated with smooth muscle and juxtaglomerular cells of the arteriolar vessels also contained dopa decarboxylase, but this enzyme was not present in any of the peritubular axons. Our results are compatible with the possibility that, in the rat, the juxtaglomerular blood vessels, but not the renal tubules, are supplied by dopaminergic as well as by noradrenergic nerves.

Animals↗
PubMed1999

Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter.

Mice lacking the dopamine transporter (DAT) display biochemical and behavioural dopaminergic hyperactivity despite dramatic alteration in dopamine homeostasis. In order to determine the anatomical and functional integrity of the dopaminergic system, we examined the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine synthesis as well as DOPA decarboxylase and vesicular monoamine transporter. TH-positive neurons in the substantia nigra were only slightly decreased (-27.6 +/- 4.5%), which can not account for the dramatic decreases in the levels of TH and dopamine that we previously observed in the striatum. TH mRNA levels were decreased by 25% in the ventral midbrain with no modification in the ratio of TH mRNA levels per cell. However, TH protein levels were decreased by 90% in the striatum and 35% in the ventral midbrain. In the striatum, many dopaminergic projections had no detectable TH, while few projections maintained regular labelling as demonstrated using electron microscopy. DOPA decarboxylase levels were not modified and vesicular transporter levels were decreased by only 28.7% which suggests that the loss of TH labelling in the striatum is not due to loss of TH projections. Interestingly, we also observed sporadic TH-positive cell bodies using immunohistochemistry and in situ hybridization in the striatum of homozygote mice, and to some extent that of wild-type animals, which raises interesting possibilities as to their potential contribution to the dopamine hyperactivity and volume transmission previously reported in these animals. In conjunction with our previous findings, these results highlight the complex regulatory mechanisms controlling TH expression at the level of mRNA, protein, activity and distribution. The paradoxical hyperdopaminergia in the DAT KO mice despite a marked decrease in TH and dopamine levels suggests a parallel to Parkinson's disease implying that blockade of DAT may be beneficial in this condition.

Animals↗
PubMed1980

Role of dopamine storage function in the control of rat striatal tyrosine hydroxylase activity.

Pretreatment of rats with reserpine prevents and post-treatment with RO4-1284 depletes the gamma-butyrolactone (GBL)-induced increase of striatal dopamine (DA) levels. This suggests that the accumulation of DA in striatal nerve endings that normally follows GBL-induced cessation of nigrostriatal impulse flow is in reserpine-sensitive sites. Three days after a single injection of reserpine, the ability of either haloperidol, a DA receptor blocker, or GBL to enhance DA synthesis is greatly reduced and these responses recover slowly over a two week period. Similarly, the ability of haloperidol to elevate striatal DA metabolite concentrations shows a similar pattern of inhibition. The rate of recovery after reserpine of haloperidol effects on DA metabolite concentrations and the activation of striatal tyrosine hydroxylase (measured in vivo by the 30 min L-DOPA accumulation after decarboxylase inhibition with NSD-1015) after either haloperidol or GBL parallels the rate of recovery of basal DA levels. The accumulation of DA after GBL proceeds for 60 min before beginning to plateau in normal rats, but 3 days after reserpine the DA elevation stops after 15 min and lasts for only 30 min in 10 day reserpinized animals. The initial 15 min accumulation of DA after GBL is the same in normal, 3 day and 10 day reserpinized rats, indicating that the initial enzymic rate of activity is the same, but the duration of activation is less. Thus, inhibition of DA storage function by reserpine alters the coupling of DA autoreceptor activity with tyrosine hydroxylase activity. It is suggested that DA storage function modulates tyrosine hydroxylase activity by controlling the amount of DA available for attachment to and inhibition of tyrosine hydroxylase enzyme. This hypothesis is consistent with recent immunocytochemical observations which suggest an association of tyrosine hydroxylase with synaptic vesicles in DA neuronal terminal areas.

4-Butyrolactone↗
PubMed1981

Transformation of catecholaminergic precursors into glucagon (A) cells in mouse embryonic pancreas.

In embryonic mice, the catecholamine biosynthetic enzyme tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] can be visualized immunocytochemically in a population of cells in epithelial cords of the developing pancreas. These embryonic catecholamine cells, first seen by day 11, are large and vacuolated and have a folded nuclear membrane. One day later, at day 12, glucagon is first detected immunocytochemically in pancreatic cells similar in location and morphology to the embryonic catecholamine cells. By use of a method for detecting both antigens in the same cell, both the hydroxylase and glucagon can be visualized between day 12 and day 14 in 10-40% of stained cells. From day 14, the number of cells stained for hydroxylase decreases; they cannot be detected after day 18. In contrast, the cells containing glucagon increase during development and persist throughout life. Endocrine cells of the embryonic pancreas also contain dopa decarboxylase but not dopamine-beta-hydroxylase or phenylethanolamine-N-methyl transferase. In adult mice, small cells containing tyrosine hydroxylase but differing in location and morphology from the embryonic catecholaminergic cells are seen in pancreatic islets. The adult catecholaminergic cells never store glucagon. We suggest that adult glucagon (A)-containing cells arise from transformation in situ of cells that transiently express a catecholaminergic (probably dopaminergic) phenotype. These results suggest that one class of peptidergic cells may arise from transformation of an aminergic precursor.

Animals↗
PubMed2001

p-Hydroxyphenylacetate decarboxylase from Clostridium difficile. A novel glycyl radical enzyme catalysing the formation of p-cresol.

The human pathogenic bacterium Clostridium difficile is a versatile organism concerning its ability to ferment amino acids. The formation of p-cresol as the main fermentation product of tyrosine by C. difficile is unique among clostridial species. The enzyme responsible for p-cresol formation is p-hydroxyphenylacetate decarboxylase. The enzyme was purified from C. difficile strain DMSZ 1296(T) and initially characterized. The N-terminal amino-acid sequence was 100% identical to an open reading frame in the unfinished genome of C. difficile strain 630. The ORF encoded a protein of the same size as the purified decarboxylase and was very similar to pyruvate formate-lyase-like proteins from Escherichia coli and Archaeoglobus fulgidus. The enzyme decarboxylated p-hydroxyphenylacetate (K(m) = 2.8 mM) and 3,4-dihydroxyphenylacetate (K(m) = 0.5 mM). It was competitively inhibited by the substrate analogues p-hydroxyphenylacetylamide and p-hydroxymandelate with K(i) values of 0.7 mM and 0.48 mM, respectively. The protein was readily and irreversibly inactivated by molecular oxygen. Although the purified enzyme was active in the presence of sodium sulfide, there are some indications for an as yet unidentified low molecular mass cofactor that is required for catalytic activity in vivo. Based on the identification of p-hydroxyphenylacetate decarboxylase as a novel glycyl radical enzyme and the substrate specificity of the enzyme, a catalytic mechanism involving ketyl radicals as intermediates is proposed.

Acetyltransferases↗