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)

Extracellular recordings from the supraoptic nucleus of the rat established that vasopressinergic neurosecretory cells were excited by stimulation of cervical but not abdominal vagal afferents. This response was absent or significantly attenuated after microinjection of gamma-aminobutyric acid into a region of the caudal medulla known to contain the A1 noradrenaline cell group. Consistent with the possible involvement of the A1 group, vagal stimulation approximately doubled the frequency of proto-oncogene expression in A1 noradrenaline neurons, as indicated by the occurrence of nuclear Fos-like immunoreactivity in tyrosine hydroxylase-positive neurons of the caudal ventrolateral medulla. Finally, A1 region microinjection of either the N-methyl-D-aspartic acid (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV), or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), significantly reduced vasopressin cell responses to vagal stimulation. These findings suggest that: (i) the A1 group is an essential component in a pathway which relays facilitatory vagal input of cardiopulmonary origin to neurosecretory vasopressin cells, and (ii) the activation of A1 neurons in this pathway involves both NMDA and non-NMDA excitatory amino acid receptors, an observation consistent with an input to A1 cells which generates 'mixed' excitatory postsynaptic potentials.
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PMID:A1 neurons and excitatory amino acid receptors in rat caudal medulla mediate vagal excitation of supraoptic vasopressin cells. 145 Sep 50

In mouse, rat, and monkey, N-methyl-D,L-aspartic acid (NMDA) modulates gonadotropin releasing hormone (GnRH) release by an unknown mechanism. In previous studies we found that normal male mice consistently responded to NMDA administration with increased levels of plasma LH, as did most normal female mice and female hypogonadal mice with fetal preoptic area implants (HPG/POA). To investigate the mechanism of NMDA-induced GnRH release, immunocytochemistry of c-fos protein (FOS) was used for detection of neurons activated by NMDA administration. In both normal male and HPG/POA mice, FOS expression was unchanged in GnRH cells after NMDA administration. That neurosecretory cells can respond to NMDA was shown by the induction of FOS in many CRH (corticotropin-releasing hormone) cells in the paraventricular nucleus. Immunocytochemistry of beta-Endorphin, neuropeptide Y, tyrosine hydroxylase, an enzyme marker for catecholaminergic neurons, and glutamic acid decarboxylase, an enzyme marker for GABA neurons, was combined with that for FOS in normal male mice. Many noradrenergic (NA) neurons in the locus coeruleus (32-61%), and dopaminergic (DA) neurons in the mediobasal hypothalamus (15-31%) expressed FOS after NMDA administration while FOS was only rarely induced in neurons with the other neuromodulators tested. FOS was also induced in the locus coeruleus in male (43, 54%) and female (40, 55, 69%) HPG/POA mice. In contrast, few cells of the locus coeruleus expressed FOS in normal or HPG/POA mice after saline challenge. These results suggested that NMDA did not activate GnRH cells directly, but that NA neurons in the locus coeruleus were activated by NMDA and might be involved in stimulating GnRH release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Norepinephrine neurons in mouse locus coeruleus express c-fos protein after N-methyl-D,L-aspartic acid (NMDA) treatment: relation to LH release. 168 42

We measured biochemical markers of excitability in brain excised for neurosurgical therapy of epilepsy. Intraoperative electrocorticography was used to identify and compare samples from regions of persistent interictal spike discharges and areas of the cerebral convexity which were free of interictal spiking. We found that interictal spiking was associated with elevated tissue levels of the excitatory amino acids glutamic acid (26%, p less than 0.001) and aspartic acid (25%, p less than 0.05). There was also a significant increase in the activity of the enzymes glutamic acid dehydrogenase (20%, p less than 0.01) and aspartate acid aminotransferase (18%, p less than 0.01) which are involved in their formation. There was no change in the levels of the inhibitory neurotransmitters GABA or taurine. We also found a significant increase in the activity of tyrosine hydroxylase (52%, p less than 0.001), the rate controlling enzyme in catecholamine biosynthesis. There was a reduction in the density (Bmax) of cortical alpha-1 adrenoceptors (26%, p less than 0.01) and a concomitant diminution of receptor coupled phosphatidylinositide metabolism (21%, p less than 0.01). This blunting of inhibitory noradrenergic transmembrane signaling may contribute to a relative imbalance between excitatory and inhibitory mechanisms in epileptogenic neocortex.
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PMID:Biochemical markers of excitability in human neocortex. 177 85

Neurochemical alterations, which may be associated with the development of diabetic retinal dysfunction, were investigated using streptozotocin (STZ)-induced hyperglycemia in rats. Young male Wistar rats, weighing 100-150 g, were made diabetic with daily intraperitoneal injections of STZ (30 mg/kg) for 5 days. This treatment caused a continuous hyperglycemia (400-600 mg/dl) and suppressed gain in body weight. Nine weeks after the STZ treatment, a significant increment in retinal valine and a decline in phenylalanine were noted, while the concentrations of other neuroactive amino acids, such as gamma-aminobutyric acid and aspartic acid, in the retina remained unchanged. On the other hand, the concentration of retinal dopamine (DA) was found to decrease significantly from the third week of hyperglycemia, when [3H]spiperone binding showed a tendency to increase in the retinal particulate fraction. However, the activities of tyrosine hydroxylase and aromatic L-amino acid decarboxylase (AADC) and the uptake of [3H]tyrosine showed no alteration in the retina of diabetic rats. The accumulation rate of 3,4-dihydroxyphenylalanine (DOPA) in vivo in the retina of diabetic rats, measured following the administration of the AADC inhibitor m-hydroxybenzyl-hydrazine (100 mg/kg i.p.), was also unchanged. Although [3H]DA uptake by retinal tissue was similar in control and diabetic animals, the spontaneous efflux of [3H]DA from the retina was found to be significantly accelerated in STZ-treated animals. In addition, the release of preloaded [3H]DA, elicited by repeated photic stimulation, was significantly attenuated in retina from diabetic rats. These results suggest that an accelerated efflux of DA, possibly leading to the depletion of DA from the retinal DA system, may account for early retinal dysfunctions known to occur in diabetic subjects.
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PMID:Alterations in the retinal dopaminergic neuronal system in rats with streptozotocin-induced diabetes. 392 83

The neurotoxic effect of glutamate in cultured mouse mesencephalic dopaminergic neurons was investigated. Neuron-rich cell cultures were prepared from 13-14-day-old fetal mouse ventral mesencephalic tissue. Cultures were exposed to glutamate for 10 min and evaluated for glutamate neurotoxicity (GNT) 18-24 hr later by tyrosine hydroxylase (TH) immunostaining, microtubule associated protein-2 (MAP2) immunostaining, and radiolabeled dopamine uptake assay. In glutamate-exposed cultures, the number of TH-positive neurons and the level of dopamine uptake were reduced to 40% (35-45%) and 50% (47-52%), respectively, of control cultures. The number of MAP2-positive neurons was also reduced to 47%, indicating that the GNT was not restricted or selective to dopaminergic neurons. It is concluded that GNT was mediated by the N-methyl-D-aspartic acid (NMDA) receptor from the following observations: 1) GNT was completely blocked by MK-801, an NMDA receptor antagonist; 2) NMDA itself was as toxic as glutamate; 3) 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate (AMPA/KA) receptor, did not block GNT; 4) kainate did not show neurotoxicity at a low concentration; and 5) two modulators of the NMDA receptor, 7-chlorokynurenic acid and magnesium, were effective in blocking GNT. Protective effects of phorbol myristate acetate, a tumor promoter, and gangliosides (GM1 and GT1b) on GNT were also demonstrated. Possible interactions between GNT and several protein kinase cascades were also investigated. Forskolin, an activator of adenyl cyclase and protein kinase A, showed some protective effect on GNT. But okadaic acid, an inhibitor of phosphatases, and genistein, a tyrosine kinase inhibitor, did not show any protective effect. These results suggest that 1) glutamate is capable of causing neuronal death in the substantia nigra; 2) GNT on dopaminergic neurons is mainly mediated by the NMDA receptor under the conditions of our study; 3) protein kinase C translocation is a key mechanism of GNT; and 4) there is an interplay of a signal transduction system in the pathomechanism of GNT.
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PMID:Glutamate neurotoxicity in mesencephalic dopaminergic neurons in culture. 790 39

In mesencephalic primary cultures derived from E14 rat embryos, calretinin- and tyrosine hydroxylase-immunoreactive neurons comprised 2% and 5% of the total cell population, respectively, at 6-7 days in vitro. The number of calretinin-immunoreactive neurons was unchanged after a 12- or 24-h exposure to 500 microM kainic acid (KA), but a 50% cell loss was detected after a 48-h exposure to KA. Tyrosine hydroxylase-immunoreactive neurons demonstrated a 50% and 67% cell loss at 24- and 48-h exposures to 500 microM KA. A 500 microM N-methyl-D-aspartic acid (NMDA) incubation for 24 h had no effect on calretinin-immunoreactive cell number, but did significantly reduce tyrosine hydroxylase-immunoreactive cell numbers by 26%. In tyrosine hydroxylase-immunoreactive cells, exposure to KA appeared to stimulate the retraction of the neuritic tree and to cause somatic swelling. In contrast, calretinin-immunoreactive neurons developed larger and more complex neuritic trees after a 24-h exposure to 500 microM KA but not NMDA. Immunohistochemical colocalization studies revealed that all tyrosine hydroxylase-immunoreactive and the majority of calretinin-immunoreactive neurons expressed the glutamate receptor subunits GluR2-R3. Very low levels of NMDAR1 receptor subunits were detected on cells in this culture and GluR4 receptor subunits were not detectable. Our experiments showed that glutamate receptors present in both calretinin- and tyrosine hydroxylase-immunoreactive cells were functional, since phosphorylated cAMP/Ca2+ response element-binding protein levels were increased in both cell types after 10 or 30 min exposures to 500 microM KA. The present results indicate that in the mesencephalic cultures tyrosine hydroxylase-immunoreactive cells are more vulnerable to KA excitotoxicity than calretinin-immunoreactive neurons.
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PMID:Differential effects of excitatory amino acids on mesencephalic neurons expressing either calretinin or tyrosine hydroxylase in primary cultures. 901 46

The role of glutamate as a neurotransmitter in the zebrafish olfactory bulb (OB) was established by examining neuronal activation following 1). glutamate receptor agonist stimulation of isolated olfactory bulbs and 2). odorant stimulation of intact fish. Four groups of neurons (mitral cells, projection neurons; granule cells, juxtaglomerular cells, and tyrosine hydroxylase-containing cells; interneurons) were identified on the basis of cell size, cell location, ionotropic glutamate receptor (iGluR) agonist/odorant sensitivity, and glutamate, gamma-aminobutyric acid (GABA), and tyrosine hydroxylase immunoreactivity. Immunoreactive glutamate levels were highest in olfactory sensory neurons (OSNs) and mitral cells, the putative glutamatergic neurons. The sensitivity of bulbar neurons to iGluR agonists and odorants was established using a cationic channel permeant probe, agmatine (AGB). Agmatine that permeated agonist- or odor-activated iGluRs was fixed in place with glutaraldehyde and detected immunohistochemically. N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA)/kainic acid (KA) iGluR agonists and odorants (glutamine, taurocholic acid) stimulated activity-dependent labeling of bulbar neurons, which was blocked with a mixture of the iGluR antagonists, D-2-amino-5-phosphono-valeric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The AMPA/KA antagonist CNQX completely blocked glutamine-stimulated AGB labeling of granule cells and tyrosine hydroxylase-containing cells, suggesting that, in these cell types, AMPA/KA receptor activation is essential for NMDA receptor activation. However, blocking AMPA/KA receptor activity failed to eliminate AGB labeling of mitral cells or juxtaglomerular cells. Collectively, these findings indicate that glutamate is the primary excitatory neurotransmitter in the zebrafish OB and that iGluR subtypes function heterogeneously in the bulbar neurons.
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PMID:Odor-stimulated glutamatergic neurotransmission in the zebrafish olfactory bulb. 1244 20

Glutamate is the dominant excitatory neurotransmitter in a large number of physiological processes including neuroendocrine regulation. Some pharmacological studies have shown that different subtypes of glutamate receptor, such as the N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methy-4-isoxazolepropionic acid (AMPA) receptors, are involved in stress-induced adrenocorticotropin (ACTH) and prolactin secretion. However, the roles of the respective glutamate receptors and the mechanism of ACTH and prolactin secretion during stress via these receptors have not been investigated in detail. In the present study, we evaluated the role of AMPA-type glutamate receptor in ACTH and prolactin regulation under restraint stress in adult male rats. Male rats pretreated with a selective AMPA receptor antagonist, 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX; 50 microg), through a lateral ventricle cannula were stressed by immobilization. Administration of NBQX inhibited ACTH and prolactin secretion in response to restraint stress. However, NBQX had no significant effects on the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine biosynthesis, as measured by the accumulation of 3, 4-dihydroxyphenylalanine (DOPA). In addition, administration of NBQX suppressed stress-induced prolactin secretion in the male rats pretreated with alpha-MT, an inhibitor of dopamine synthesis, and infused with dopamine solution (2.5 microg/200 microl/10 min). These results indicated that the effects of NBQX on prolactin secretion might be mediated by non-dopamine mechanisms. The contents of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the median eminence (ME) of the male rats decreased during restraint stress; however, the fluctuations in CRH and AVP were eliminated by NBQX administration. These results suggest that stress-induced ACTH and prolactin release mediated by neurotransmission via AMPA receptors might be partly attributable to hypophysiotropic regulatory factors in the hypothalamus.
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PMID:Inhibition of stress-induced adrenocorticotropin and prolactin secretion mediating hypophysiotropic factors by antagonist of AMPA type glutamate receptor. 1727 25

The clinical symptoms of Parkinson's disease (PD) appear late and only when the degenerative process at the level of the nigrostriatal dopamine (DA) pathway is quite advanced. An increase in brain-derived neurotrophic factor (BDNF) expression may be one of the molecular signals associated to compensatory and plastic responses occurring in basal ganglia during presymptomatic PD. In the present study, we used in vivo microdialysis, semiquantitative reverse transcriptase-polymerase chain reaction, and immunohistochemistry to study N-methyl-D-aspartic acid (NMDA) receptor regulation of BDNF expression in substantia nigra (SN) of adult rats after partial lesioning of the nigrostriatal DA pathway with unilateral striatal injections of 6-hydroxydopamine (6-OHDA). A time-dependent partial decrease of striatal DA tissue content as well as parallel and gradual increases in extracellular glutamate and aspartate levels in SN were found 1 to 7 days after unilateral 6-OHDA intrastriatal injection. Instead, the number of tyrosine hydroxylase-immunoreactive (IR) cells in the ipsilateral SN pars compacta remained statistically unchanged after neurotoxin injection. Intrastriatal administration of 6-OHDA also produced an early and transient augmentation of pan-BDNF, exon II-BDNF, and exon III-BDNF transcripts in the ipsilateral SN. The pan-BDNF and exon II-BDNF transcript increases were completely abolished by the prior systemic administration of MK-801, a selective antagonist of NMDA receptors. MK-801 also blocked the increase in BDNF-IR cells in SN observed 7 days after unilateral 6-OHDA intrastriatal injections. Our findings suggest that a coupling between glutamate release, NMDA receptor activation, and BDNF expression may exist in the adult SN and represent an important signal in this midbrain nucleus triggered in response to partial DA loss occurring in striatal nerve endings during presymptomatic PD.
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PMID:NMDA receptors mediate an early up-regulation of brain-derived neurotrophic factor expression in substantia nigra in a rat model of presymptomatic Parkinson's disease. 1932 33

We have previously shown that the multi-functional phosphoprotein osteopontin (OPN) is present in the substantia nigra (SN) and that its mRNA and protein expression are up-regulated following toxic insult. We now report the effects of the arginine-glycine-aspartic acid (RGD)-containing peptide fragment of OPN and OPN inactivation on the survival of tyrosine hydroxylase (TH) positive neurones in primary rat ventral mesencephalic (VM) cultures and in SN in the rat. Treatment of VM cultures with the fragment of OPN containing the RGD integrin binding domain did not decrease TH positive cell number, but instead the peptide fragment protected against cell loss induced by both MPP(+) and lipopolysaccharide (LPS). Incorporation of an OPN antibody into VM cultures caused a concentration-dependent loss of TH positive neurones. The OPN antibody also exacerbated MPP(+) - and LPS-induced cell loss at all concentrations tested. In the rat, administration of the RGD-containing peptide fragment of OPN protected TH positive neurones against a mechanically-induced lesion and against 6-hydroxydopamine- and LPS-induced cell loss. The protection against 6-hydroxydopamine toxicity was confirmed in a separate study using stereological analysis. By contrast, stereotaxic injection of the OPN antibody into the SN resulted in a loss of TH positive cells. These results suggest that OPN may be necessary for the survival of TH positive cells in SN but through the RGD-containing peptide fragment may also have neuroprotective properties relevant to Parkinson's disease.
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PMID:The RGD-containing peptide fragment of osteopontin protects tyrosine hydroxylase positive cells against toxic insult in primary ventral mesencephalic cultures and in the rat substantia nigra. 2062 61


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