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)

Immunohistochemical and pharmacological techniques were used to examine perivascular nerves, endothelium and the effects of inhibition of nitric oxide synthesis on responses in mesenteric arteries/perfused mesenteric arterial beds of the Golden hamster. Frequency-dependent vasoconstrictions to electrical field stimulation and dose-dependent vasoconstrictions to noradrenaline were significantly augmented by NG-nitro-L-arginine methyl ester (10(-5) M), an inhibitor of nitric oxide synthase. In preparations with tone raised with methoxamine (10 microM) dose-dependent relaxations to ATP, but not to acetylcholine, were blocked by NG-nitro-L-arginine methyl ester. In the presence of guanethidine (5 microM) to block sympathetic neurotransmission there was no neurogenic relaxation to electrical field stimulation. Furthermore, the sensory neurotoxin capsaicin (0.05-5 nmol) did not elicit relaxation. Immunohistochemical studies demonstrated dense plexuses of fibres immunoreactive for tyrosine hydroxylase and neuropeptide Y, a plexus of moderate density for calcitionin gene-related peptide and an absence of fibres immunoreactive for substance P and vasoactive intestinal polypeptide. Of particular interest is the finding that whereas sympathetic perivascular nerves and nitric oxide regulate the function of hamster mesenteric arteries, there is no apparent motor function of calcitonin gene-related peptide-containing sensory nerves.
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PMID:Innervation and nitric oxide modulation of mesenteric arteries of the golden hamster. 899 11

A population of neurons in the anterior substantia nigra pars compacta of the guinea-pig display an outward K+ conductance, which can be activated by a brief period of hypoxia, and blocked in a dose-dependent manner by tolbutamide (100-500 microns): these features are those of an ATP-sensitive K+ channel (KATP). Typically hyperpolarisation of the cell is accompanied by a mean decrease in input resistance (IR) of 41.29 +/- 3.69 M omega (SEM), a mean decrease in resting membrane potential (RMP) of 8.58 +/- 2.41 mV and a cessation of action potential generation. These cells do not show positive immunoreactivity for tyrosine hydroxylase (TH), but they are present in slices that contain TH and release dopamine (DA). Given the intimacy of these cells with nigral DA systems, and given the fact that they have D2 receptors and respond to dopaminergic (DAergic) agents, it was of interest to see if lesions of DAergic neurons had any effect on the above response. The neurotoxin 6-hydroxy dopamine (6-OHDA) was injected into the median forebrain bundle to destroy the DAergic neurons of the nigrostriatal pathway. Unilateral lesion of this pathway produced a significant reduction in the above conductance, in the lesioned substantia nigra pars compacta (SNpc) (mean IR decrease of only 17.99 +/- 4.44 M omega (and a mean RMP decrease of 1.40 +/- 1.76 mV), whilst the hypoxia induced change in potential on the non-lesioned side was still marked and indistinguishable from that in control animals. The KATP channel would therefore appear to be under the influence of the DAergic neurons of the SNpc.
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PMID:6-Hydroxy dopamine lesions block a tolbutamide-sensitive K+ conductance in the guinea-pig substantia nigra. 913 73

The effects of hibernation on mesenteric arterial innervation and function were examined using pharmacological and immunohistochemical techniques in age-matched controls, cold-exposed controls, and 4-wk-hibernated golden hamsters. Electrical field stimulation of the isolated mesenteric arterial bed elicited frequency-dependent vasoconstriction. The sensitivity of responses was significantly increased in tissues from hibernating animals compared with cold-exposed controls. Vasoconstrictor responses to exogenous norepinephrine were also increased in hibernation. However, there was a significant decrease in sensitivity of vasoconstriction to ATP in hibernated and cold-exposed tissue compared with age-matched controls. In preparations preconstricted with methoxamine, endothelium-dependent vasodilator responses to acetylcholine and ATP were similar among the groups. Immunohistochemical investigation of mesenteric arteries revealed no differences among the groups in density of innervation by nerves immunoreactive for tyrosine hydroxylase, neuropeptide Y, and calcitonin gene-related peptide. Postjunctional changes appear to occur in hibernation, leading to augmentation of sympathetic vasoconstriction, which is consistent with the increase in peripheral vascular resistance in hibernation. Endothelium-dependent vasodilatation is not significantly changed in hibernation in the hamster mesenteric arterial bed.
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PMID:Effects of hibernation on neural and endothelial control of mesenteric arteries of the golden hamster. 924 85

The protein kinases and protein phosphatases that act on tyrosine hydroxylase in vivo have not been established. Bovine adrenal chromaffin cells were permeabilized with digitonin and incubated with [gamma-32P]ATP, in the presence or absence of 10 microM Ca2+, 1 microM cyclic AMP, 1 microM phorbol dibutyrate, or various kinase or phosphatase inhibitors. Ca2+ increased the phosphorylation of Ser19 and Ser40. Cyclic AMP, and phorbol dibutyrate in the presence of Ca2+, increased the phosphorylation of only Ser40. Ser31 and Ser8 were not phosphorylated. The Ca2+-stimulated phosphorylation of Ser19 was incompletely reduced by inhibitors of calcium/calmodulin-stimulated protein kinase II (46% with KN93 and 68% with CaM-PKII 273-302), suggesting that another protein kinase(s) was contributing to the phosphorylation of this site. The Ca2+-stimulated phosphorylation of Ser40 was reduced by specific inhibitors of protein kinase A (56% with H89 and 38% with PKAi 5-22 amide) and protein kinase C (70% with Ro 31-8220 and 54% with PKCi 19-31), suggesting that protein kinases A and C contributed to most of the phosphorylation of this site. Results with okadaic acid and microcystin suggested that Ser19 and Ser40 were dephosphorylated by PP2A.
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PMID:Tyrosine hydroxylase phosphorylation in digitonin-permeabilized bovine adrenal chromaffin cells: the effect of protein kinase and phosphatase inhibitors on Ser19 and Ser40 phosphorylation. 937 70

Whole-cell patch clamp recordings were made in a pontine slice preparation of the rat brain containing the nucleus locus coeruleus (LC). In a first series of experiments, it was demonstrated that tyrosine hydroxylase-positive LC neurons of young (10-14 days of age) rats are multipolar with numerous dendrites. When pipettes filled with the marker molecule biocytin were used for recording, all cells exhibiting outward current responses to noradrenaline (100 microM) showed the morphology typical for LC neurons. At a holding potential of -80 mV, noradrenaline (100 microM) produced a comparably small outward current both in LC neurons of young (8-14 days) and older (18-23 days) rats. In contrast, 2-methylthio ATP (2-MeSATP; 100 microM) caused a relatively small inward current in the young animals, while inward current responses were much larger in most older animals (8 out of a total of 11). It is suggested that after birth there are probably no functional P2 purinoceptors present at LC neurons. Thereafter, P2 purinoceptor-function increases with age, reaching maturity only in animals older than 18 days.
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PMID:Differential age-dependent expression of alpha2 adrenoceptor- and P2 purinoceptor-functions in rat locus coeruleus neurons. 952 93

Select groups of neurons within the brain alter their firing rate when ambient glucose levels change. These glucose-responsive neurons are integrated into systems which control energy balance in the body. They contain an ATP-sensitive K+ channel (KATP) which mediates this response. KATP channels are composed of an inwardly rectifying pore-forming unit (Kir6.1 or Kir6.2) and a sulfonylurea binding site. Here, we examined the anatomical distribution and phenotype of cells containing Kir6.2 mRNA within the rat brain by combinations of in situ hybridization and immunocytochemistry. Cells containing Kir6. 2 mRNA were widely distributed throughout the brain without apparent concentration in areas known to contain specific glucose-responsive neurons. Kir6.2 mRNA was present in neurons expressing neuron-specific enolase, tyrosine hydroxylase, neuropeptide Y (NPY) and the glutamic acid decarboxylase isoform, GAD65. No astrocytes expressing glial fibrillary acidic protein or oligodendrocytes expressing carbonic anhydrase II were found to co-express Kir6.2 mRNA. Virtually all of the NPY neurons in the hypothalamic arcuate n. and catecholamine neurons in the substantia nigra, pars compacta and locus coeruleus contained Kir6.2 mRNA. Epinephrine neurons in the C2 area also expressed high levels of Kir6.2, while noradrenergic neurons in A5 and A2 areas expressed lower levels. The widespread distribution of Kir6.2 mRNA suggests that the KATP channel may serve a neuroprotective role in neurons which are not directly involved in integrating signals related to the body's energy homeostasis.
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PMID:Distribution and phenotype of neurons containing the ATP-sensitive K+ channel in rat brain. 983 37

Systemic administration of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) produces parkinsonism in experimental animals by a mechanism involving impaired energy production. MPTP is converted by monoamine oxidase B to 1-methyl-4-phenylpyridinium (MPP+), which blocks complex I of the electron transport chain. Oral supplementation with creatine or cyclocreatine, which are substrates for creatine kinase, may increase phosphocreatine (PCr) or cyclophosphocreatine (PCCr) and buffer against ATP depletion and thereby exert neuroprotective effects. In the present study we found that oral supplementation with either creatine or cyclocreatine produced significant protection against MPTP-induced dopamine depletions in mice. Creatine protected against MPTP-induced loss of Nissl and tyrosine hydroxylase immunostained neurons in the substantia nigra. Creatine and cyclocreatine had no effects on the conversion of MPTP to MPP+ in vivo. These results further implicate metabolic dysfunction in MPTP neurotoxicity and suggest a novel therapeutic approach, which may have applicability for Parkinson's disease.
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PMID:Creatine and cyclocreatine attenuate MPTP neurotoxicity. 1022 17

In the dt(sz) mutant hamster with idiopathic generalized dystonia, functional abnormalities of several neurotransmitters have been suggested to play a role in the development of symptoms. In the present study, we have used histochemistry with (35)S-ATP labeled oligonucleotides to determine whether these abnormalities are associated with modulation in the expression of neurotransmitter genes in motor regions. We examined the expression of genes encoding cholecystokinin (CCK), somatostatin (SRIF), thyrotropin-releasing hormone (TRH), glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43) in the cortex and basal ganglia of dystonic hamsters and of non-dystonic control hamsters of a related inbred line and of a non-related outbred line. The distribution of these mRNAs in normal hamster brain was similar to that in normal rat brain. In all cortical regions studied (frontal, parietal and piriformis), the expression of CCK was similar in dystonic and inbred controls but was significantly greater than in outbred controls. In the anterior thalamus, CCK expression was lower in dystonic hamsters than in both control groups. SRIF expression was significantly decreased in the cortex and striatum of dystonic animals than in inbred and outbred control hamsters. GAD expression was lower in the striatum and substantia nigra, pars reticulata of dystonic than in outbred hamsters, but similar values were found in all groups in the other regions studied. TH was lower in the substantia nigra of dystonic than in inbred controls. No changes were found in GAP43 expression. This study demonstrates that changes in modulation of the expression of some peptides and neurotransmitter enzymes can be found in the dystonic hamster, which is in contrast to other animal models such as the dystonic rat, where no such changes have been found. The present data are consistent with previous findings in dt(sz) hamsters that suggest a dysfunction within the basal ganglia-thalamocortical circuits.
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PMID:Expression of cholecystokinin, somatostatin, thyrotropin-releasing hormone, glutamic acid decarboxylase and tyrosine hydroxylase genes in the central nervous motor systems of the genetically dystonic hamster. 1055 May 8

Pituitary adenylate cyclase-activating polypeptide (PACAP-27) was incubated in a tyrosine hydroxylase (TyrOH) assay with a homogenate preparation of the nucleus accumbens of the rat. TyrOH activity was determined in vitro by measuring the production of L-dopa with HPLC-ECD. Only in the presence of adenosine nucleotides (ATP, App(NH)p) PACAP-27 increased TyrOH activity with a EC(50)of 100 nM. Since the PACAP-27 effect on TyrOH was abolished when homogenate or pellet of the nucleus accumbens were coincubated with CHAPS, the peptide effect appears to be receptor mediated. TyrOH activation produced by PACAP-27 increased in the presence of the phosphodiesterase inhibitor papaverine indicating the involvement of cAMP. The marked effect of the non-hydrolysable adenosine nucleotide App(NH)p also supports a cAMP-dependent TyrOH activation not related to ADP or an ADP-dependent mechanism. This report's data suggest that PACAP-27 activates TyrOH in the rat nucleus accumbens through receptor-mediated cAMP formation. The exact receptor type present in the nucleus accumbens has yet not been specified.
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PMID:Pituitary adenylate cyclase-activating polypeptide (PACAP-27) enhances tyrosine hydroxylase activity in the nucleus accumbens of the rat. 1065 30

Sulfonylureas block ATP-dependent K(+) channels (K/ATP channels) in pancreatic beta cells and brain gamma-aminobutyric acid (GABA) containing neurons causing depolarization-evoked insulin or GABA release. In high concentrations, sulfonylureas also inhibit catecholamine release from bovine adrenal chromaffin cells and isolated guinea pig aorta. In this study, we examined the effect of glipizide, a sulfonylurea, on dopamine release from PC12 cells and found that neither basal nor K(+)-stimulated dopamine release was affected. Although PC12 cells expressed mRNA for the K/ATP channel, functional K/ATP channels could not be demonstrated electrophysiologically, consistent with the lack of effect of glipizide on dopamine release. Glipizide did, however, increase cytoplasmic retention of the acidic dopamine metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), indicating blockade of their outward transport. The cellular accumulation of DOPAC was accompanied by reduced tyrosine hydroxylase activity and reduced formation of dopamine and its metabolites presumably by a negative feedback effect of the increased cytoplasmic concentrations of DOPAC.
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PMID:Effect of glipizide on dopamine synthesis, release and metabolism in PC12 cells. 1066 6


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