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)

At neutral (7.0) and slightly basic (8.2) pH, L-3,4-dihydroxyphenylalanine (L-DOPA), 3,4,5-trihydroxyphenylalanine (5-OH-DOPA) and 3,4-dihydroxyphenylethylamine (dopamine) undergo autoxidation. The binding of radiolabeled oxidation products of L-DOPA, 5-OH-DOPA and dopamine to membrane proteins was compared by a filtration procedure. Membranes from tentacles of the sea anemone Metridium senile bind significantly more 5-OH-DOPA than L-DOPA and dopamine. Membranes from rat brain and brains from the three-spined stickleback Gasterosteus aculeatus, bind significantly more dopamine than L-DOPA and 5-OH-DOPA. Membranes from Metridium contain an o-diphenol O2: oxidoreductase (tyrosinase). In the absence of inhibitors, enzymatic oxidation causes a fiftyfold increase in binding of L-DOPA and a more than tenfold increase in binding of dopamine, whereas the binding of 5-OH-DOPA only is increased by 10%. It is concluded than 5-OH-DOPA more easily undergo autoxidation than L-DOPA and dopamine, but its quinone form is probably less reactive with membrane proteins. The suitability of tyrosinase-mediated biosynthesis of L-DOPA and 5-OH-DOPA versus tyrosine hydroxylase-mediated biosynthesis of L-DOPA and dopamine in primitive nervous systems and in the vertebrate CNS is discussed on the basis of the cytotoxic potential through irreversible binding to membrane proteins of oxidation products of the catechol compounds formed.
J Neural Transm Gen Sect 1990
PMID:3,4-Dihydroxyphenylethylamine, L-3,4-dihydroxyphenylalanine and 3,4,5-trihydroxyphenylalanine: oxidation and binding to membranes. A comparative study of a neurotransmitter, a precursor and a neurotransmitter candidate in primitive nervous systems. 197 46

An immunohistological analysis of the chromaffin cell system of the American eel revealed the presence of tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) in all cells. However, phenylethanolamine-N-methyltransferase (PNMT) was seen only in a fraction of the chromaffin cells. This suggests the presence of both norepinephrine and epinephrine cells and the absence of specific dopamine cells. The chromaffin cells are most numerous in the anterior region of the posterior cardinal vein, where they occupy a subendothelial position. Their number decreases caudally, and a relatively small number are present in the larger veins of the opisthonephric kidney. No PNMT-positive cells were identified in this region, although a radioenzymatic assay had previously shown the presence of epinephrine. Methionine-enkephalin immunoreactivity seems to be restricted to the chromaffin cells. However, particularly large amounts of leucine immunoreactivity occur in the interrenal cells, with smaller quantities in the chromaffin cells. The chromaffin cells of the eel also contain morphine immunoreactivity.
Gen Comp Endocrinol 1990 Sep
PMID:Catecholamines, opioid peptides, and true opiates in the chromaffin cells of the eel: immunohistochemical evidence. 198 Feb 50

Mesocortical dopamine (DA) neurons projecting to the prefrontal and cingulate cortices possess a faster basal firing rate and exhibit more bursting than other midbrain DA neurons. Thus, we examined whether tyrosine administration could preferentially affect DA synthesis in these DA neurons. Tyrosine administered at doses as low as 25 mg/kg significantly increased in vivo tyrosine hydroxylation in the prefrontal and cingulate cortices without affecting it in other mesocortical, mesolimbic, and nigrostriatal DA terminal fields examined. Further studies in the mesoprefrontal DA neurons showed that tyrosine administered at higher doses of 50 mg/kg initially enhanced tyrosine hydroxylation and elevated endogenous DA levels within 60 min. The resultant increases in DA levels appeared to feedback and normalize prefrontal tyrosine hydroxylase activity. The levels of DA metabolites in the prefrontal cortex were unaltered by doses of tyrosine from 25-200 mg/kg, suggesting that the functional transmitter outflow from these DA neurons is not normally affected by precursor administration under resting conditions. However, when these mesocortical DA neurons were pharmacologically activated following administration of the anxiogenic beta-carboline, FG7142, tyrosine administration (25 mg/kg) was effective in increasing DA metabolite levels in the prefrontal cortex. These results thus suggest that enhanced activity of the mesoprefrontal DA neurons renders these DA neurons much more dependent up on tyrosine availability for maintenance of transmitter output.
J Neural Transm Gen Sect 1990
PMID:Mesocortical dopamine neurons: high basal firing frequency predicts tyrosine dependence of dopamine synthesis. 236 11

The effect of acute and chronic administration of cocaine on the sympathetic nervous system in the cardiac tissue and the adrenal glands of rats were studied. Both with acute and chronic administration of the drug, the concentration-response curve to (-)-norepinephrine on the isolated rat atria was shifted to the right, with a lower pD2. The endogenous ventricular norepinephrine levels remain unchanged after acute injections of cocaine, but when the drug was administered chronically, the endogenous neurotransmitter content were augmented about 50%. The tyrosine hydroxylase activity in atria and adrenal homogenates decreased after chronic injections of cocaine, while it was not observed any modifications in the enzyme activity after acute administrations of the drug.
Gen Pharmacol 1985
PMID:Effects of cocaine on several adrenergic system parameters. 285 32

The in vivo and in vitro effects of TRH on tyrosine hydroxylase activity and on endogenous levels of noradrenaline as an index of noradrenergic neurons activity were studied in rat hypothalamus. The hydroxylation of tryptophan and the liberation of 5-hydroxyindole acetic acid were analyzed as an index of serotoninergic activity. TRH had no effect on tyrosine hydroxylase from hypothalamic homogenates in concentrations up to 100 ng/ml. Neither was the hydroxylation of tyrosine in intact hypothalamus. The TRH (4 micrograms/kg) decreased 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine accumulation after 10 min, and no effect on serotonin and noradrenaline concentrations was observed. TRH decreased endogenous levels of 5-hydroxyindole acetic acid by 35%. Thus, the results show that TRH or TSH might play a role in a short-loop feedback action involving catecholaminergic and serotonergic nerve terminals that regulate the liberation of TRH.
Gen Pharmacol 1987
PMID:Effects of TRH on hypothalamic catecholaminergic and serotoninergic neurons. 288 96

1. Single injection of haloperidol (2 mg/kg, i.p.) or chlorpromazine (10 mg/kg, i.p.) produced an activation of dopamine synthesis and turnover as evidenced by increased activity of tyrosine hydroxylase and higher levels of homovanillic acid in the striatum of rats. 2. The endogenous concentration of dopamine remained unchanged in striatum and other brain regions examined, except in hippocampus where it was slightly (20%), but significantly decreased by acute haloperidol treatment. 3. In contrast, long-term treatment with neuroleptics over a period of 21 days decreased the synthesis and turnover of dopamine in the striatum. Whereas short-term treatment with chlorpromazine and haloperidol produced marked sedation, chronic treatment enhanced spontaneous locomotor activity by 20 and 26% and sniffing frequency by 19 and 24%, respectively. 4. Our data demonstrate that tolerance develops to the stimulating effect of haloperidol and chlorpromazine on striatal dopamine turnover. This adaptive change might be responsible for the emergence of clinical effects. 5. It is suggested that after repeated treatment, "chemical denervation" occurs as a result of chronic blockade of dopaminergic transmission in the striatum and that the proliferation of dopamine receptors (i.e. supersensitivity) is probably responsible for hyperactivity and overt sniffing behaviour.
Gen Pharmacol 1982
PMID:Comparative effects of short- and long-term treatment with neuroleptics on behavioural activity as well as dopamine turnover in striatum. 612 Aug 80

1. The present paper is concerned with some pharmacological actions of ionophore A-23187 on both isolated guinea-pig atria and cat's nictitating membrane. 2. The drug showed an agonist effect on both tissues. 3. There is an indirect effect by releasing catecholamines which is antagonized by reserpine and beta receptor blockers in atria and alfa receptor blockers in nictitating membrane. 4. The ionophore exhibited a direct positive chronotropic effect on the atria. This effect is blocked by Ca2+ flux antagonist such as verapamil and pentobarbital and not by reserpine. 5. Ionophore produced no direct effect on the activity of the isolated tyrosine hydroxylase but showed an inhibitory action in intact tissues, mediated by released of endogenous catecholamines, since this effect is antagonized by reserpine. 6. Monoamine oxidase activity was unaffected by ionophore.
Gen Pharmacol 1982
PMID:Pharmacological effects of ionophore A-23187 on isolated guinea-pig atria and isolated cat nictitating membrane. 612 79

Acute effects of lithium chloride upon the parameters of central noradrenergic function were assessed at either a therapeutic dose (2 m-equiv/kg) or a toxic one (10 m-equiv/kg) on rats. Lithium chloride lacked a direct effect on tyrosine hydroxylase (TH), monoamine oxidase (MAO), or catechol-O-methyltransferase (COMT) in concentrations up to 2 mM. A single i.p. injection of both studied doses inhibited MAO a hr later. Endogenous NA levels in frontal cerebral cortex were increased by a therapeutic dose and slightly increased by a toxic dose. Uptake of [3H]NA was increased in pretreated tissues at a therapeutic level but decreased by a toxic dose. The unmetabolized [3H]NA was always increased over controls.
Gen Pharmacol 1984
PMID:Acute effects of lithium chloride on noradrenergic neurons from rat cerebral cortex. 614 81

A neuropharmacologic approach was utilized to investigate the catecholaminergic influence on the hypothalamic regulation of growth hormone (GH) secretion in young (6-week-old) male domestic fowl. The selective inhibition of norepinephrine (NE) and epinephrine (E) synthesis or activity by diethyldithiocarbamate (DDC), FLA63 (dopamine-beta-hydroxylase inhibitors), phenoxybenzamine (alpha 1 receptor blocker), and yohimbine (alpha 1 and alpha 2 receptor antagonist) was associated with a decline in circulating GH levels. Similarly inhibition of NE reuptake by imipramine or desmethylimipramine were followed by reduced GH secretion. In the presence of alpha-methyl-p-tyrosine (alpha Mpt, a tyrosine hydroxylase inhibitor), the administration of phenylephrine (alpha 1 agonist) was followed by increased plasma concentrations of GH. However, alone, it was without effect. Similarly plasma concentrations of GH were elevated by dihydroxyphenylserine (DOPS, a precursor of NE/E) in chicks pretreated with DDC or carbidopa. These data are consistent with the stimulatory hypothalamic control of GH involving NE/E which exert their effects via alpha (probably alpha 1) postsynaptic stimulatory receptors. Evidence that it is E rather than NE, which is the catecholamine involved or the hypothalamic control of GH, comes from the decrease in plasma GH concentration following the inhibition of central E synthesis by SKF64139 (an inhibitor of phenylethanolamine-N-methyltransferase). Some evidence for a limited inhibitory dopaminergic system was found. Inhibition of dopamine (DA) synthesis by alpha Mpt produced significant elevations in plasma GH concentration. In addition, apomorphine (DA agonist) consistently depressed GH release. However, blockade of DA receptors by pimozide had either no effect on plasma GH concentrations or at a very high dose decreased plasma GH concentrations. NE/E also appear to have a depressive effect on plasma concentrations of GH in young chicks, probably via a peripheral site of action. Plasma concentrations of GH were reduced by the peripheral administration of NE, which might be expected not to cross the blood-brain-barrier (BBB), alpha 1/alpha 2 agonists clonidine and p-amino clonidine (which does not cross BBB), NE/E precursors L-DOPA and DOPS, and the beta agonist, isoproterenol. Furthermore, the depression of peripheral E synthesis (by SKF29661 which inhibits phenylethanolamine-N-methyltransferase) elevated the plasma concentration of GH.
Gen Comp Endocrinol 1984 Jun
PMID:Catecholamine involvement in the control of growth hormone secretion in the domestic fowl. 673 52

The endocrine cells and nerves of the respiratory tract of the reptile Podarcis hispanica were investigated by immunocytochemistry under light microscopy. Immunoreactivities were more numerous in the lung than in the trachea. In the tracheal epithelium, endocrine cells immunoreactive to PHI, PYY, and Leu-enkephalin were detected, while immunoreactivity to serotonin, calcitonin, CGRP, PHI, and Leu-enkephalin was found in pulmonary endocrine cells. Numerous nerve fibers positive to NSE, PGP9.5, chromogranin, tyrosine hydroxylase, calcitonin, CGRP, bombesin, substance P, VIP, NPY, and PYY were found in the lungs. In addition, neurons positive to NSE and PGP9.5 were also found. Immunoreactivities to PHI and PYY in cells and to NSE, PGP9.5, chromogranin, tyrosine hydroxylase, calcitonin, CGRP, and PYY in nerves, were reported first in the respiratory system of reptiles.
Gen Comp Endocrinol 1994 Dec
PMID:An immunocytochemical study of the respiratory system of Podarcis hispanica (Reptilia). 753 37


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