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)

The concept that a neurone may release transmitter from both dendritic and axonal sites was investigated by studying mesolimbic dopaminergic neurones. The rat ventral tegmentum (containing dendrites and somata of mesolimbic dopaminergic neurones) possessed high levels of dopamine and tyrosine hydroxylase. Slices of ventral tegmentum accumulated [3H]dopamine (15 or 60 nM) and stimulus-induced release of [3H]dopamine was observed after elevated potassium (44 mM). The potassium-induced release was calcium-dependent. These dopaminergic parameters were compared to those found for nucleus accumbens (containing terminals of mesolimbic dopaminergics neurones). Thioridazine and clozapine elevated 3,4-dihydroxyphenylacetic acid (DOPAC) concentration in ventral tegmentum.
 ...
PMID:Mesolimbic dopaminergic neurones and somatodendritic mechanisms. 4 96

The electrical properties and the possible regulation of these properties were studied by means of intracellular microelectrode recordings in cells of mouse neuroblastoma clone N1E-115. This clone has high levels of tyrosine hydroxylase and regulates this enzyme. Cells treated for 24 h with 4 muM aminopterin followed by at least 5 days in culture developed rhythmic discharge of action potentials when superfused with phosphate-buffered saline containing less than 0.2 mM calcium or less than 0.2 mM calcium and zero potassium. This ionic excitation occurred in no cells at less than 5 days after treatment with aminopterin but at 5 days or more after treatment, 20% of cells responded to low calcium while 52% responded to low calcium and zero potassium. Concomitant with the development of a susceptibility to ionic excitation was an increase in the average resting membrane potential and morphologic maturation. This ionic excitation of cultured mouse neuroblastoma cells may be useful for studying biochemical events associated with repetitive discharge of action potentials.
 ...
PMID:Ionic excitation of a clone of mouse neuroblastoma. 23 72

Electrical stimulation of the rat locus coeruleus cases about a 300% increase in the activity of the tyrosine hydroxylase prepared from the hippocampus on the stimulated side and assayed in the presence of subsaturating concentrations of tyrosine and pteridine cofactor. Addition of calcium or cAMP to soluble preparations of tyrosine hydroxylase isolated from the hippocampus produces a similar activation of tyrosine hydroxylase. The activation of tyrosine hydroxylase produced by calcium is reversed by addition of the calcium chelator, EGTA, while the activation produced by cAMP addition or by electrical stimulation of the locus coeruleus is unaffected by addition of EGTA to the assay medium. The activation of tyrosine hydroxylase produced by electrical stimulation or by addition of calcium or cAMP to the assay medium appears to be mediated in part by alterations in the kinetic properties of the enzyme. All treatment causes the enzyme to have an increased affinity for substrate and pteridine cofactor and a decreased affinity for the endproduct inhibitor, norepinephrine. These results are suggestive that the activation of tyrosine hydroxylase which occurs during periods of increased impulse flow in noradrenergic neurons may be initiated by alterations in calcium fluxes or by changes in the steady state levels of cAMP which accompany neuronal depolarization.
 ...
PMID:Tyrosine hydroxylase: allosteric activation induced by stimulation of central noradrenergic neurons. 24 Jan 33

Tyrosine hydroxylase activity was measured in high speed supernatants obtained from full thickness segments of aganglionic and ganglionic colon of three children with Hirschsprung's disease. Tyrosine hydroxylase activity expressed as pmole DOPA/mg protein/min was 0.93 +/- 0.16 in ganglionic and 2.67 +/- 0.21 in aganglionic colon. Tyrosine hydroxylase activity in ganglionic colon rose to 2.29 +/- 0.11 following calcium stimulation (100 muM) but could not be further increased in aganglionic colon. Addition of norepinephrine (2 X 10(-4) M) to tissue homogenates inhibited tyrosine hydroxylase activity in ganglionic colon by 57 +/- 8% but only by 14 +/- 3% in aganglionic colon, suggesting that the enzyme present in aganglionic colon is insensitive to feedback inhibition by endogenous norepinephrine. The elevation of tyrosine hydroxylase activity in aganglionic colon and its insensitivity to calcium stimulation and norepinephrine inhibition is further evidence of sympathetic overactivity in the aganglionic colon and suggests a basic enzymatic abnormality in the pathogenesis of Hirschsprung's disease.
 ...
PMID:Sympathetic neurotransmitter metabolism in Hirschsprung's disease. 24 82

The effects of depolarizing concentrations of veratridine were studied to determine the degree to which dopamine synthesis stimulation was correlated with stimulated endogenous dopamine release in rat brain striatal synaptosomes. Incubations included cocaine and pargyline to prevent dopamine reuptake and metabolism, respectively. Veratridine produced a 44% increase in dopamine release in 10 minutes and a similar increase in synthesis rate. Preincubation with tetrodotoxin prevented the increase in both release and synthesis, while incubation in a calcium-free medium antagonized both responses approximately 50%. Addition of 1 mM ethylene glycol bis(beta-aminoethylether)-N, N'-tetraacetic acid to the calcium-free incubation medium further inhibited the release response, but not the synthesis stimulation. These results indicate that, in general, the degree of synthesis stimulation produced by depolarizing agents such as veratridine can be correlated with their stimulation of dopamine release, suggesting either 1)that transmitter release itself is a signal for synthesis stimulation, possibly by removal of feedback inhibition of tyrosine hydroxylase or 2) that depolarizing agents increase synthesis through a secondary metabolic change that is either caused by, or at least accompanied by, transmitter release.
 ...
PMID:Dopamine synthesis in rat brain striatal synaptosomes. I. Correlations between veratridine-induced synthesis stimulation and endogenous dopamine release. 126 35

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)
 ...
PMID:Regulation of the chromaffin granule catecholamine transporter in cultured bovine adrenal medullary cells: stimulus-biosynthesis coupling. 127 22

We previously reported the partial purification and characterization of a toxic substance (sea urchin toxin) isolated from the pedicellariae of the sea urchin Toxopneustes pileolus (Nakagawa and Kimura, Jpn J Pharmacol 32: 966-968, 1982). In the present study, we examined the effect of sea urchin toxin on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Sea urchin toxin inhibited the secretion of catecholamines stimulated by carbachol and nicotine but not by veratridine or a high concentration of K+. The toxin inhibited the carbachol-evoked influx of 22Na+ and 45Ca2+ at concentrations similar to those for catecholamine secretion. The inhibition of catecholamine secretion by sea urchin toxin was not overcome by increasing the concentration of carbachol. Preincubation of cells with the toxin caused a time-dependent inhibition in the secretion stimulated by carbachol even when the toxin was removed from the incubation medium. The toxin suppressed catecholamine synthesis and tyrosine hydroxylase activity in carbachol-stimulated cells. In addition, sea urchin toxin inhibited [3H]phencyclidine binding to adrenal medullary cells whereas it did not alter cyclic GMP accumulation caused by muscarine. Further purified fractions from sea urchin toxin by concanavalin A affinity column chromatography also inhibited carbachol-evoked secretion of catecholamines. These results suggest that sea urchin toxin inhibits carbachol-enhanced secretion and synthesis of catecholamines by suppression of nicotinic acetylcholine receptor-mediated Na+ influx and subsequent Ca2+ influx in cultured adrenal medullary cells.
 ...
PMID:Inhibition of nicotinic acetylcholine receptor-mediated secretion and synthesis of catecholamines by sea urchin toxin in cultured bovine adrenal medullary cells. 128 Apr 35

A brain-specific multifunctional calmodulin-dependent protein kinase, calmodulin-dependent protein kinase IV, which exhibited characteristic properties quite different from those of calmodulin-dependent protein kinase II, was purified approximately 230-fold from rat cerebellum. The purified preparation gave two protein bands with molecular weights of 63,000 (alpha) and 66,000 (beta) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, both of which showed protein kinase activity as examined by the activity gel method. The molecular weight of the enzyme was estimated as about 67,000 from sedimentation coefficient (3.2 S) and Stokes radius (50 A), indicating a monomeric structure of the enzyme. The enzyme phosphorylated smooth muscle myosin light chain, synapsin I, microtubule-associated protein 2, tau protein, myelin basic protein, histone H1, and tyrosine hydroxylase in a Ca2+/calmodulin dependent manner, suggesting that the enzyme is a multifunctional calmodulin-dependent protein kinase capable of phosphorylating a large number of substrates. A synthetic peptide, Lys-Ser-Asp-Gly-Gly-Val-Lys-Lys-Arg-Lys-Ser-Ser-Ser-Ser, was found to be a specific substrate for this kinase and, using this peptide as substrate, the distribution of the enzyme activity in various rat tissues was examined. The activity was found in cerebral cortex, brain stem, and cerebellum, most abundantly in cerebellum, but other tissues tested, including liver, spleen, kidney, lung, heart, skeletal muscle, and adrenal gland showed very little activity.
 ...
PMID:Purification and characterization of a brain-specific multifunctional calmodulin-dependent protein kinase from rat cerebellum. 130 65

Tryptic digestion of tyrosine hydroxylase (TH) isolated from rat adrenal glands labeled with 32Pi produced five phosphopeptides. Based on the correspondence of these phosphopeptides with those identified in TH from rat pheochromocytoma cells, four phosphorylation sites (Ser8, Ser19, Ser31, and Ser40) were inferred. Field stimulation of the splanchnic nerves at either 1 or 10 Hz (300 pulses) increased 32P incorporation into TH. At 10 Hz, the phosphorylation of Ser19 and Ser40 was increased, whereas at 1 Hz, Ser19, Ser31, and Ser40 phosphorylation was increased. Stimulation at either 1 or 10 Hz also increased the catalytic activity of TH, as measured in vitro (pH 7.2) at either 30 or 300 microM tetrahydrobiopterin. Nicotine (3 microM, 3 min) increased Ser19 phosphorylation, vasoactive intestinal polypeptide (10 microM, 3 min) increased Ser40 phosphorylation, and muscarine (100 microM, 3 min) increased TH phosphorylation primarily at Ser19 and Ser31. Vasoactive intestinal polypeptide, but not nicotine or muscarine, mimicked the effects of field stimulation on TH activity. Thus, the regulation of rat adrenal medullary TH phosphorylation by nerve impulses is mediated by multiple first and second messenger systems, as previously shown for catecholamine secretion. However, different sets of second messengers are involved in the two processes. The action of vasoactive intestinal polypeptide as a secretagogue involves the mobilization of intracellular calcium, whereas its effects on TH phosphorylation are mediated by cyclic AMP. This latter effect of vasoactive intestinal polypeptide and the consequent increase in Ser40 phosphorylation appear to be responsible for the rapid activation of TH by splanchnic nerve stimulation.
 ...
PMID:Activation and multiple-site phosphorylation of tyrosine hydroxylase in perfused rat adrenal glands. 134 70

We have studied the action of glutamate on striatal tyrosine hydroxylase activity and determined which type of glutamate receptors are involved. Glutamate stimulated (EC50 = 4 +/- 2 microM) the activity of tyrosine hydroxylase in slices of rat neostriatum. The selective N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (10 microM) blocked the stimulation; however, both the non-NMDA receptor antagonist glutamate diethyl ester (10 microM) and the general excitatory amino acid antagonist kynurenate (10 microM) had no effect. NMDA was even more potent than glutamate in stimulating tyrosine hydroxylase activity. Quisqualate (100 microM) only slightly stimulated the enzyme, and kainate had practically no effect. Omission of Mg2+ from the incubation medium potentiated the glutamate stimulation. Neither tetrodotoxin nor atropine prevented the stimulation. These results suggest that glutamate stimulates striatal tyrosine hydroxylase activity via NMDA receptors. The lack of effect of tetrodotoxin and atropine suggests that glutamate acts on NMDA receptors located on the dopaminergic nigrostriatal terminal. The stimulation may involve the entry of Ca2+ into the terminal through the NMDA receptor ionophore, since a Ca(2+)-free medium or cadmium totally blocked the stimulation of the enzyme by glutamate.
 ...
PMID:Glutamate stimulation of tyrosine hydroxylase is mediated by NMDA receptors in the rat striatum. 134 45


1 2 3 4 5 6 7 8 9 10 Next >>