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)

The transsynaptic induction of the monoamine transporter present on the membrane of chromaffin granules was studied in primary cultures of dissociated bovine adrenomedullary cells submitted to a chronic secretory stimulation. The amount of the vesicular monoamine transporter was assayed by binding of the specific ligand [3H]-dihydrotetrabenazine. After several days of incubation in the presence of high potassium, the concentration of [3H]-dihydrotetrabenazine binding sites was increased by a 1.5-2.5 factor. This increase was smaller in the presence of the cholinergic agonist carbachol. The long-term inductions of the vesicular monoamine transporter, of tyrosine hydroxylase, and of acetylcholinesterase were of similar magnitude. Under the same conditions, we found no variation in either the activities of other catecholamine biosynthetic enzymes (dopamine beta-hydroxylase and DOPA decarboxylase), or in metabolic enzymes such as lactate dehydrogenase and cytochrome c oxidase, and a decrease in the cellular content of chromogranin A and cytochrome b-561. The induction of the vesicular monoamine transporter was inhibited by the calcium channel antagonists, fluspirilene and nifedipine, and was increased by the agonist Bay K 8644. It was abolished by cycloheximide and actinomycin D. These results indicate that calcium entry into chromaffin cells increases the synthesis of the vesicular monoamine transporter, presumably by transcriptional activation. Elevation of intracellular cyclic AMP concentration or activation of protein kinase C also induced an increase in the expression of the vesicular monoamine transporter. Our results confirm that components of storage vesicle membranes are differentially regulated in response to secretory stimulation, as are several cytosolic or intravesicular soluble proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of the chromaffin granule catecholamine transporter in cultured bovine adrenal medullary cells: stimulus-biosynthesis coupling. 127 22

Bovine adrenomedullary chromaffin (BAMC) cells, cultured in a defined medium, were used to study the mechanisms of toxicity and cellular resistance to the catecholamine neuron toxicants 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+). The viability of the cells was assessed biochemically [cellular catecholamine content and the catalytic activities of tyrosine hydroxylase (TH) and lactate dehydrogenase (LDH)] and anatomically (by electron microscopy). When cultures of BAMC cells were exposed to MPTP or MPP+ for 3 days, a marked loss of cellular catecholamines and TH activity was observed. The addition of an inhibitor of monoamine oxidase (MAO) B (Ro 19-6327), but not MAO A (clorgyline), prevented the toxicity of MPTP but not that of MPP+. In addition, the cellular toxicity of MPP+, but not MPTP, was antagonized by desmethylimipramine, an inhibitor of cellular catecholamine uptake. The toxicity of MPP+ was time dependent, with losses of TH and the release of cellular LDH occurring after 48 h in culture. Catecholamine depletion occurred somewhat sooner, being evident after 24 h of exposure to MPP+. The cellular toxicity of MPP+ was concentration dependent and significantly enhanced by inhibitors of catecholamine vesicular uptake (reserpine, tetrabenazine, or Ro 4-1284). Electron microscopic examination of cells treated with either MPP+, tetrabenazine, or their combination revealed that MPP+ damaged BAMC cells and that this damage was markedly potentiated by the inhibition of vesicular uptake by tetrabenazine. The concentration of glucose in the culture media of untreated cells slowly decreased as a function of time. The rate of glucose consumption was markedly accelerated by MPP+ treatment and the losses in cell TH and the release of LDH into the media were preceded by a 99% depletion of glucose from the media. In cultures not treated with MPP+, lactate accumulated in the media as a function of time. Addition of MPP+ to the media increased the formation of lactate, in a concentration-dependent manner. Reserpine pretreatment further enhanced the production of lactate in response to MPP+. Culturing cells in glucose-free medium greatly potentiated the effects of MPP+ on cellular TH and catecholamines. The toxicity observed after 3 days' exposure of BAMC cells to MPP+ could be prevented when the medium was replaced with fresh medium every 24 h. The effects of glucose deprivation and reserpine were observed to be additive. The ability of MPP+ to affect mitochondrial function is determined by the capacity of the storage vesicle to sequester the pyridinium, acting as a cytosolic "buffer."(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanisms of toxicity and cellular resistance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium in adrenomedullary chromaffin cell cultures. 197 91

The effects of retinoic acid (RA), a naturally occurring metabolite of vitamin A, on the growth, morphology and neurochemical differentiation of the PC12 clone of rat pheochromocytoma cells were investigated. RA added to the medium inhibited the growth of PC12 cells in a dose-dependent manner up to 10 microM without affecting their morphology. In PC12 cells cultured in the presence of 10 microM RA for 8 days, the specific activity of choline acetyltransferase (ChAT) was increased 2-fold, while the specific activity of tyrosine hydroxylase (TH) was decreased 0.5-fold compared with cells cultured in the absence of RA. Specific activities of acetylcholinesterase (AChE), glutamate decarboxylase (GAD) and lactate dehydrogenase (LDH) were not affected by RA. Both the increase of ChAT and the decrease of TH induced by RA exhibited similar time and dose dependencies. RA inhibited the increase of TH activity induced by nerve growth factor (NGF), an adrenergic neuronotrophic factor on PC12 cells. From these observations it was concluded that RA induces a cholinergic neurochemical differentiation of PC12 cells independent of a morphological differentiation.
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PMID:Cholinergic differentiation of clonal rat pheochromocytoma cells (PC12) induced by retinoic acid: increase of choline acetyltransferase activity and decrease of tyrosine hydroxylase activity. 257 10

Synaptosomes prepared from striatum or cerebral cortex of rat brain were incubated with antibodies raised against three neurotransmitter biosynthetic enzymes, choline acetyltransferase, glutamate decarboxylase and tyrosine hydroxylase in the presence or absence of complement. Immunolysis was first assessed by measuring the release of lactic dehydrogenase or reduction in potassium from synaptosomes, and lysis of neurochemically specific subpopulation of synaptosomes was detected by measuring release of either transmitters, their biosynthetic enzymes or by blockade of sodium-dependent uptake of transmitter or precursor. In both striatum and cortex, antibodies to choline acetyltransferase lysed only cholinergic while those against glutamate decarboxylase only lysed GABAergic nerve terminals. Antibodies against tyrosine hydroxylase lysed only the dopaminergic terminals in striatum but not noradrenergic terminals in cortex. The lysis occurred only in the presence of complement, and was never observed in the absence of complement. The studies indicate that antibodies to the neurotransmitter biosynthetic enzymes recognize antigens in the synaptosomal membrane specific only to neurons harboring the transmitters. The results suggest that the antibody-positive peptides in the membrane and neurotransmitter biosynthetic enzyme share common antigenic sites, probably common peptides.
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PMID:Evidence for specific immunolysis of nerve terminals using antisera against choline acetyltransferase, glutamate decarboxylase and tyrosine hydroxylase. 286 53

We have investigated the effects of substrate-bound laminin on levels of enzymes of the catecholamine biosynthetic pathway in primary cultures of calf adrenal chromaffin cells. Laminin increases the levels of the enzymes tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenylethanolamine-N-methyl-transferase. This effect is selective, in that levels of other enzymes (lactate dehydrogenase, aromatic amino acid decarboxylase, and acetylcholinesterase) are not increased. The effect of laminin can be blocked by antibodies directed against a fragment of the heparin-binding domain of the molecule, whereas antibodies directed against other fragments do not block the increase in tyrosine hydroxylase. Thus the laminin domain involved in enzyme regulation in chromaffin cells is apparently the same as that previously implicated in laminin's interactions with neurons to potentiate survival and stimulate neurite outgrowth (Edgar, D., R. Timpl, and H. Thoenen, 1984, EMBO (Eur. Mol. Biol. Organ.) J., 3:1463-1468). The increase in chromaffin cell tyrosine hydroxylase levels is preceded by an activation of the enzyme in which the Vmax (but not the Km) is altered. The effects of laminin appear to be developmentally regulated, since neither activation nor increased levels of tyrosine hydroxylase occur in adult adrenal chromaffin cells exposed to laminin.
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PMID:Laminin increases both levels and activity of tyrosine hydroxylase in calf adrenal chromaffin cells. 286 97

An antiserum to dopamine-beta-hydroxylase purified from bovine adrenal medulla, acting in the presence of complement, caused the release of 12% of lactate dehydrogenase, 20% of tyrosine hydroxylase activity, and 40% of noradrenaline (NA) content from synaptosomes prepared from rat brain cerebral cortex. Uptake of [3H]NA was reduced by 54%. Anti-serum alone or complement alone were without action. The antiserum plus complement had no effect on choline uptake and did not release choline acetyltransferase, glutamate decarboxylase, dopamine or 5-hydroxytryptamine. These results suggest selective lysis of noradrenergic terminals had occurred. An enhancement of lysis was not observed when synaptosomes were stimulated with 75 mequiv./lK+ and exposed to a sub-maximal dose of antiserum, plus complement.
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PMID:Specific lysis of noradrenergic synaptosomes by an antiserum to dopamine-beta-hydroxylase. 287 56

The neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can induce degeneration of dopamine (DA) and other central monoamine neurons, leading to Parkinson's disease-like effects in man, monkey, and mouse. MPTP and other substituted phenylpiperidines related to synthetic analgesics including alphaprodine and meperidine were evaluated for potency vs. uptake of 0.1 microM tritiated DA, norepinephrine (NE), or serotonin (5HT) in synaptosomal preparations of mouse striatum or cerebral cortex. The most potent inhibitor of the uptake of 3H-DA was N-methyl-4-phenylpyridinium ion (MPP+; IC50 = 1 microM, Ki = 0.4 microM), a metabolite of MPTP; its effect was competitive and reversible. Other analogs of MPTP: the N-ethylindole AHR-1709, N,N-dimethyl-MPTP, and N-methyl-4-phenylpiperidine were all more potent than MPTP against 3H-DA uptake. N-dealkylation and N-propyl substitution, as well as pyridine ring substitution, decreased affinity for DA uptake while 3',4'-dihydroxyphenyl substitution increased potency and selectivity for catecholamine uptake, and quarternarization of the pyridine ring also increased potency against DA uptake. Active compounds showed higher potency against the uptake of NE than of DA. MPP+ was also more potent than MPTP in releasing endogenous DA from striatal synaptosomes (EC50 = 3 vs. 30 microM), but did not release the cytoplasmic markers tyrosine hydroxylase and lactate dehydrogenase (LDH). In contrast to MPTP, synthetic phenylpiperidine analgesics, their potential metabolites and the experimental neuroleptic agent AHR-1709 all failed to deplete striatal DA in vivo, even if active in vitro against DA uptake.
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PMID:Synthetic analgesics and other phenylpiperidines: effects on uptake and storage of dopamine and other monoamines mouse forebrain tissue. 349 Jun 12

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

An antiserum raised to nerve terminal sacs derived from the electric organ and Torpedo marmorata was used to lyse guinea pig brain synaptosomes in the presence of complement. From the release of the cytoplasmic enzymes choline acetyltransferase, lactate dehydrogenase, tyrosine hydroxylase and glutamate decarboxylase it appears that the antiserum binds specifically to cholinergic terminals. The amount of lactate dehydrogenase released was used to estimate the proportion of cholinergic nerve terminals in different synaptosome preparations.
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PMID:Quantitation of cholinergic synaptosomes from guinea pig brain. 611 35

Linear sucrose density gradient centrifugation of a crude synaptosomal-mitochondrial preparation of rat striatum was performed at 82,500g for 7.5, 15 and 30 min and 1, 4 and 20 h. After centrifugation various marker enzyme activities were measured throughout the gradients, viz. tyrosine hydroxylase (TH) and DOPA decarboxylase (DD) as markers of dopaminergic synaptosomes, lactate dehydrogenase (LDH) as a general synaptosomal marker and monoamine oxidase (MAO) as a mitochondrial marker. At all centrifugation times the distribution patterns of TH and DD activity coincided almost perfectly. Notable differences were found between the sedimentation properties of these TH/DD-containing particles and LDH-containing particles: TH and DD were symmetrically distributed in the gradient much sooner than LDH, at all centrifugation times the top of the TH and DD curves was lying deeper in the gradient than the highest LDH activity, and TH and DD became enriched in the gradients to a much greater extent than LDH. It is concluded that rat striatal dopaminergic synaptosomes form a relatively homogeneous population of particles sedimenting faster into the gradients than the bulk of striatal synaptosomes does. This distinct sedimentation behaviour of the dopaminergic synaptosomes can be usefully applied for analytical purposes.
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PMID:Subcellular fractionation of striatum: sedimentation properties of dopaminergic synaptosomes. 613 70


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