Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

It was previously reported that escin Ib isolated from horse chestnut inhibited gastric emptying (GE) in mice, in which the capsaicin-sensitive sensory nerves (CPSN), the central nervous system and endogenous prostaglandins (PGs) were involved. In the present study, the possible involvement of dopamine and dopamine receptors in the inhibition of GE by escin Ib were investigated in mice. GE inhibition by escin Ib (25 mg/kg, p.o.) was attenuated after pretreatment with a single bolus of DL-alpha-methyl-p-tyrosine methyl ester (400 mg/kg, s.c., an inhibitor of tyrosine hydroxylase), reserpine (5 mg/kg, p.o., a catecholamine depletor), 6-hydroxydopamine (80 mg/kg, i.p., a dopamine depletor). Furthermore, pretreatment with spiperone (0.5-5 mg/kg, s.c., a dopamine2 receptor antagonist), haloperidol (0.5-10 mg/kg, s.c.) and metoclopramide (1-10 mg/kg, s.c.) (centrally acting dopamine2 receptor antagonists) attenuated the effect of escin Ib. Domperidone (0.1-5 mg/kg, s.c., a peripheral-acting dopamine2 antagonist) showed a weak attenuation, but SCH 23390 (1-5 mg/kg, s.c., a dopamine, receptor antagonist) did not. It is postulated that escin Ib inhibits GE, at least in part, mediated by CPSN, to stimulate the synthesis and/or release of dopamine, to act through central dopamine2 receptor, which in turn causes the release of PGs.
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PMID:Possible involvement of dopamine and dopamine2 receptors in the inhibitions of gastric emptying by escin Ib in mice. 1113 4

The use of fetal astrocytes for gene delivery into brains with neurodegenerative diseases has been suggested. Therefore, the effects of neurotransmitters in the brain on such cells are of interest. The presence of D1(D1A) receptors and the effect of dopamine on a fetal human astrocyte cell line (SVG cells) in vitro were examined. SVG cells expressed D1(D(1A)), but not D5(D1B) receptors, as shown by RT-PCR. Exposure to dopamine, apomorphine, and the specific D1 agonist, SKF-38393, increased glial-derived neurotrophic factor production of SVG cells, as well as intracellular free calcium. Exposure to the specific D1 antagonist, SCH 23390, blocked these effects. Thus, if implanted into a brain region rich in dopamine, or if transfected with the tyrosine hydroxylase gene, fetal astrocytes may serve as paracrine/autocrine cells capable of supplying critical growth factors to diseased brain tissue.
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PMID:Dopamine increases glial cell line-derived neurotrophic factor in human fetal astrocytes. 1118 May 11

Previous studies have shown that dopamine (DA) may play an important role in mediating or modulating the facilitating action of clozapine in glutamatergic transmission. This possibility was tested further in the present study by pharmacological manipulation of the DA system. When rats were pretreated with reserpine (which blocks storage of biogenic amines) and alpha-methyl para-tyrosine (AMPT, which inhibits tyrosine hydroxylase, the rate-limiting enzyme for the DA synthesis), the ability of clozapine to augment glutamatergic transmission in pyramidal cells of the medial prefrontal cortex (mPFC) was totally abolished. Furthermore, the application of l-dihydroxyphenylalanine (L-DOPA, the immediate precursor of DA which bypasses the synthesis step inhibited by AMPT) reversed the effect produced by reserpine plus AMPT and reinstated the facilitating action of clozapine, whereas administration of 5-hydroxytryptophan (5-HTP), the immediate precursor of 5-HT, was ineffective. In addition, DA D1 receptor antagonist SCH 23390 also completely prevented clozapine-induced facilitating action in the mPFC pyramidal cells. The present results demonstrate that newly synthesized DA and DA D1 receptors are required for clozapine to elicit its facilitating action on glutamatergic neurotransmission in the mPFC.
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PMID:Modulation of the ability of clozapine to facilitate NMDA- and electrically evoked responses in pyramidal cells of the rat medial prefrontal cortex by dopamine: pharmacological evidence. 1267 Mar 20

DOPA decarboxylase (DDC; aromatic-l-amino acid decarboxylase; EC 4.1.1.28) is absent in retinas from 6-day-old chicken embryos (E6) but is expressed in retina of E8 embryos, in the presumptive outer plexiform layer. Thereafter, DDC appears in cell bodies of presumptive amacrine cells. The dopamine (DA) content of E9/10 and E15/16 retinas, pre-incubated with l-DOPA for 1 h, increased 250- and 600-fold, respectively, showing that DDC is active since early in development. Intercellular communication, measured by endogenous cyclic AMP accumulation, was observed when retinas from E9/10 to E15/16 were pre-incubated for 1 h with 1 mm l-DOPA, washed and followed by incubation in the presence of 0.5 mm 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor. Cyclic AMP accumulation was prevented when pre-incubation with l-DOPA was carried out in the presence of carbidopa. Moreover, the accumulation of cyclic AMP was inhibited by SCH 23390 (2 micro m). The incubation of retinas in medium previously conditioned by retina-pigmented epithelium (RPE) also increased its cyclic AMP content with the characteristics described for l-DOPA. Our results show that dopaminergic communication takes place in the embryonic retina, before tyrosine hydroxylase expression, provided l-DOPA is supplied to the tissue. It also shows that RPE is a potential source of l-DOPA early in development.
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PMID:L-DOPA supply to the neuro retina activates dopaminergic communication at the early stages of embryonic development. 1280 23

We demonstrated synchronous oscillation of intracellular Ca2+ in cultured-mouse mid-brain neurons. This synchronous oscillation was thought to result from spontaneous and synchronous neural bursts in a synaptic neural network. We also examined the role of endogenous dopamine in neural networks showing synchronous oscillation. Immunocytochemical study revealed a few tyrosine hydroxylase (TH)-positive dopaminergic neurons, and that cultured neurons expressed synaptophysin and synapsin I. Western blot analyses comfirmed synaptophysin, TH, and 2 types of dopamine receptor (DR), D1R and D2R expression. The synchronous oscillation in midbrain neurons was abolished by the application of R(-)-2-amino-5-phosphonopentanoic acid (AP-5) as an N-methyl-D-aspartate receptor (NMDAR) antagonist. This result suggests that the synchronous oscillation in midbrain neurons requires glutamatergic transmissions, as was the case in previously reported cortical neurons. SCH-12679, a D1R antagonist, inhibited synchronous oscillation in midbrain neurons, while raclopride, a D2R antagonist, induced a transient increase of intracellular Ca2+ and inhibited synchronous oscillation. We consider that endogenous dopamine maintains synchronous oscillation of intracellular Ca2+ through D1R and D2R, and that these DRs regulate intracellular Ca2+in distinctly different ways. Synchronous oscillation of midbrain neurons would be a useful tool for in vitro researches into various neural disorders directly or indirectly caused by dopaminergic neurons.
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PMID:Endogenous dopamine maintains synchronous oscillation of intracellular calcium in primary cultured-mouse midbrain neurons. 1504 10

Activation of human peripheral blood mononuclear cells (PBMC) triggers endogenous production of catecholamines (CA) through protein kinase (PK) C-dependent induction of tyrosine hydroxylase (TH; EC 1.14.16.2), the first and rate-limiting enzyme in the synthesis of CA. Since CA themselves are major mediators of the neural input to the immune system, we have examined their ability to affect PKC-induced TH mRNA expression and CA production in human isolated PBMC. In T- and B-lymphocytes (but not in monocytes) the PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) (but not its inactive analogue 4alpha-phorbol-12,13-didecanoate) induced TH mRNA expression which was followed by an increase in the amount of intracellular CA. Coincubation of human PBMC with dopamine (DA) (but not with norepinephrine or epinephrine) inhibited TPA-induced TH mRNA expression. The effect of DA was concentration-dependent and was mimicked by the dopaminergic D1-like receptor agonist SKF-38393 but not by the D2-like receptor agonist bromocriptine. The D1-like antagonist SCH-23390 shifted to the right the concentration-response curves of both DA and SKF-38393, while neither the D2-like antagonist domperidone, nor the alpha1-adrenoceptor antagonist prazosin, the alpha2-adrenoceptor antagonist yohimbine, or the beta-adrenoceptor antagonist propranolol affected to any significant extent the inhibitory effect of DA. SKF-38393 also significantly reduced TPA-induced increase of intracellular CA, an effect which was antagonized by SCH-23390. It is thus suggested that in human T- and B-lymphocytes PKC activation leads to TH mRNA expression and subsequent increase of intracellular CA, which can be inhibited by D1-like receptor activation. Inhibition of intracellular CA production in human PBMC promotes cell survival through reduction of activation-induced apoptosis, and dopaminergic modulation of TH expression and intracellular CA content may thus represent a novel mechanism in the cross-talk between the nervous and the immune system as well as among immune system cells.
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PMID:Dopaminergic D1-like receptor-dependent inhibition of tyrosine hydroxylase mRNA expression and catecholamine production in human lymphocytes. 1510 39

The hph-1 mice have defective tetrahydrobiopterin biosynthesis and share many neurochemical similarities with l-dopa-responsive dystonia (DRD) in humans. In both, there are deficiencies in GTP cyclohydrolase I and low brain levels of dopamine (DA). Striatal tyrosine hydroxylase (TH) levels are decreased while the number of DA neurones in substantia nigra (SN) appears normal. The hph-1 mouse is therefore a useful model in which to investigate the biochemical mechanisms underlying dystonia in DRD. In the present study, the density of striatal DA terminals and DA receptors and the expression of D-1, D-2, and D-3 receptors, preproenkephalin (PPE-A), preprotachykinin (PPT), and nitric oxide synthase (NOS) mRNAs in the striatum and nucleus accumbens and nigral TH mRNA expression were examined. Striatal DA terminal density as judged by specific [3H]mazindol binding was not altered while the levels of TH mRNA were elevated in the SN of hph-1 mice compared to control (C57BL) mice. Total and subregional analysis of the striatum and nucleus accumbens showed that D-2 receptor ([3H]spiperone) binding density was increased while D-1 receptor ([3H]SCH 23390) and D-3 receptor ([3H]7-OH-DPAT) binding density was not altered. In the striatum and nucleus accumbens, expression of PPT mRNA was elevated but PPE-A mRNA, D-1, D-2 receptor, and nNOS mRNA were not changed in hph-1 mice compared to controls. These findings suggest that an imbalance between the direct strionigral and indirect striopallidal output pathways may be relevant to the genesis of DRD. However, the pattern of changes observed is not that expected as a result of striatal dopamine deficiency and suggests that other effects of GTP cyclohydrolase I deficiency may be involved.
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PMID:Alterations in expression of dopamine receptors and neuropeptides in the striatum of GTP cyclohydrolase-deficient mice. 1553 Aug 90

We investigated the molecular mechanisms of development to phencyclidine (PCP)-induced rewarding effect by using tyrosine hydroxylase (TH) heterozygous (TH(+/-)) mice. PCP (8 mg/kg) induced the place preference in wild-type mice pretreated with PCP (10 mg/kg/day for 28 days). The place preference induced by PCP is attenuated by 6-hydroxydopamine, a dopaminergic neurotoxin, and (+) SCH-23390, a dopamine-D1 receptor antagonist, but not by DSP-4, a noradrenergic neurotoxin, and (-) sulpiride, a dopamine-D2 receptor antagonist. In TH(+/-) mice pretreated with PCP (10 mg/kg/day for 28 days), no PCP (8 mg/kg)-induced place preference was observed. In wild-type mice pretreated with PCP, the levels of cAMP, cAMP response element binding protein (CREB), and c-fos mRNA in the nucleus accumbens were increased. The levels of cAMP, CREB, and c-fos mRNA in the nucleus accumbens were not increased by the same treatment schedule of PCP in TH(+/-) mice. These findings suggest that changes in dopaminergic and/or cAMP signal cascades induced by repeated PCP treatment play an important role in the development of PCP-induced rewarding effect.
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PMID:Involvement of signal transduction cascade via dopamine-D1 receptors in phencyclidine dependence. 1554 1

Methamphetamine (METH) is a highly addictive compound that induces toxicity of the dopamine (DA) terminals of the neostriatum. Exposure to METH induces long-term deficits in dopamine transporter (DAT) and tyrosine hydroxylase (TH) levels as well as induction of glial fibrillary acidic protein (GFAP) in the caudate putamen (CPu) and the nucleus accumbens (NAc). The primary effect of exposure to METH is elevation of the level of extracellular DA; therefore, we assessed the role of the DA D1 receptor (D1R) and neurokinin-1 receptor (NK-1R) on the expression of toxicity. METH was injected intraperitoneally (10 mg/kg) four times at 2-h intervals (an acute toxic dose), and the mice were sacrificed three days after the treatment. Exposure to METH resulted in marked reduction of DAT sites (reduced to 30 and 21% relative to control in medial and lateral aspects of the CPu) assessed by binding of [125I]RTI-121 by autoradiography or Western blot analysis. Pretreatment with the nonpeptide NK-1R antagonist WIN-51,708 (10 mg/kg) 30 min prior to the first and fourth injections of METH prevented the loss of DAT sites of the CPu. Moreover, pretreatment with WIN-51,708 also prevented the reduction of TH levels induced by METH as well as the induction of GFAP in astrocytes. Pretreatment with the D1R antagonist SCH-23390 (0.25 mg/kg) 30 min before the first and fourth injections of METH conferred partial protection on DAT sites of the CPu. These results demonstrate that receptors postsynaptic to the DA terminals of the CPu are needed in order to express the neurotoxic effects of METH on integral components of the DA terminals of the nigrostriatal projection.
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PMID:Antagonists of the neurokinin-1 or dopamine D1 receptors confer protection from methamphetamine on dopamine terminals of the mouse striatum. 1554 15

Glia represents the most numerous group of nervous system cells and CNS development and function depend on glial cells. We developed a purified Muller glia culture to investigate the expression of several neurotransmitter markers on these cells, such as dopaminergic, cholinergic, GABAergic and peptidergic receptors or enzymes, based on functional assays measuring second messenger levels or Western blot for specific proteins. Purified Muller cell culture was obtained from 8-day-old (E8) embryonic chick. Glial cells cultured for 15 days (E8C15) expressed D1A and D1B receptors mRNAs, but not D1D, as detected by RT-PCR. The binding of [3H]-SCH 23390 revealed an amount of expressed receptors around 40 fmol/mg protein. Dopamine (100 microM), PACAP (50 nM) and forskolin (10 microM) induced a 50-, 30- and 40-fold cAMP accumulation on glial cells, respectively, but not ip3 production. The dopamine-promoted cAMP accumulation was blocked by 2 microM SCH 23390. Carbachol stimulated a 3-fold ip3 accumulation. Western blot analysis also revealed the expression of tyrosine hydroxylase, L-dopa decarboxylase, PAC1 receptor, GAD67 and beta2-nicotinic receptor subunit by these cells. These results indicate that several components of neurotransmitter signaling and metabolism are found in cultured Muller cells.
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PMID:Expression of functional receptors and transmitter enzymes in cultured Muller cells. 1575 30


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