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 diverse biological effects of substance P and related peptides are mediated by multiple neurokinin receptors. The CNS sites of neurokinin receptor biosynthesis have not been fully elucidated and little is known about the regulation of neurokinin receptor gene expression. In the present study, the abundance of neurokinin-1, neurokinin-2 and neurokinin-3 receptor messenger RNAs in various rat brain regions was quantitated using a sensitive solution hybridization assay. Midbrain neurokinin receptor gene expression was then examined in detail. In situ hybridization experiments localized high levels of neurokinin-3 receptor messenger RNA to presumptive dopamine neurons, as evidenced by sensitivity to 6-hydroxydopamine lesions and the presence of tyrosine hydroxylase messenger RNA in serial sections. Lesions of nigral afferent (including substance P-containing) pathways from the caudate-putamen increased both nigral neurokinin-3 and neurokinin-1 receptor messenger RNA levels two- to three-fold. These data provide the anatomical substrate for physiological data suggesting that substance P (released from striatonigral neurons) may act on nigral cells through neurokinin-1 receptors, while the substance P co-transmitter neurokinin A may act preferentially on dopamine neurons through neurokinin-3 receptors. The magnitude of denervation-induced changes in neurokinin receptor messenger RNAs suggests significant plasticity of neurokinin receptor gene expression.
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PMID:Quantitation, cellular localization and regulation of neurokinin receptor gene expression within the rat substantia nigra. 753 3

By using a double immunocytochemical method we examined the distribution of dopaminergic neurons expressing neuromedin K receptor (NKR; NK3) in the rat brain. The distribution of NKR-like immunoreactive (-LI) neurons completely overlapped that of tyrosine hydroxylase (TH)-LI neurons in the retrorubral field (A8), substantia nigra (A9), ventral tegmental area and nucleus raphe linealis (A10). Completely or partially overlapping distributions of NKR- and TH-LI neurons were found in certain regions of the hypothalamus (A11-A15) and olfactory bulb (A16). Neurons showing both NKR- and TH-like immunoreactivities, however, were only found in A8-A10: All of the NKR-LI neurons displayed TH-like immunoreactivity, and about 71-86% of the TH-LI neurons expressed NKR-like immunoreactivity. The present results provided morphological evidence for physiological modulation of dopaminergic neurons by tachykinins through NKR in A8-A10.
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PMID:Mesencephalic dopaminergic neurons expressing neuromedin K receptor (NK3): a double immunocytochemical study in the rat 947 42

By using a double immunocytochemical method we examined the distribution of dopaminergic neurons expressing neuromedin K receptor (NKR; NK3) in the rat brain. The distribution of NKR-like immunoreactive (-LI) neurons completely overlapped that of tyrosine hydroxylase (TH)-LI neurons in the retrorubral field (A8), substantia nigra (A9), ventral tegmental area and nucleus raphe linealis (A10). Completely or partially overlapping distributions of NKR- and TH-LI neurons were found in certain regions of the hypothalamus (A11-A15) and olfactory bulb (A16). Neurons showing both NKR- and TH-like immunoreactivities, however, were only found in A8-A10: All of the NKR-LI neurons displayed TH-like immunoreactivity, and about 71-86% of the TH-LI neurons expressed NKR-like immunoreactivity. The present results provided morphological evidence for physiological modulation of dopaminergic neurons by tachykinins through NKR in A8-A10.
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PMID:Mesencephalic dopaminergic neurons expressing neuromedin K receptor (NK3): a double immunocytochemical study in the rat. 949 91

By using a double immunofluorescence method we examined the distribution of noradrenergic neurons expressing substance P receptor (NK1) or neuromedin K receptor (NK3) in the rat brainstem. The distribution of SPR-like immunoreactive (-LI) neurons completely overlapped that of tyrosine hydroxylase (TH)-LI neurons in the locus coeruleus (A6), ventrolateral and lateral reticular formation of pons (A5 and A7). Partially overlapping distribution of SPR- and TH-LI neurons were found in certain regions of the medulla oblongata (A1-A4). Neurons showing both SPR- and TH-like immunoreactivities, however, were only found in the locus coeruleus complex (A5-A7): 100% of these TH-LI neurons displayed SPR-like immunoreactivity. Neurons showing both NKR- and TH-like immunoreactivities were not detected in the aforementioned areas of brainstem. The present study has provided morphological evidence for direct physiological modulation of noradrenergic neurons by tachykinins through SPR in locus coeruleus complex (A5-A7).
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PMID:Noradrenergic neurons expressing substance P receptor (NK1) in the locus coeruleus complex: a double immunofluorescence study in the rat. 1091 24

By using a double immunofluorescence method we examined the distribution of dopaminergic neurons (A17) expressing neuromedin K receptor (NKR, NK(3)) in the rat retina. The distribution of NKR-like immunoreactive (-LI) neurons partially overlapped that of tyrosine hydroxylase (TH)-LI neurons in the inner retina of section and flat-mount preparation. Neurons showing both TH- and NKR-like immunoreactivities were found in the retina (A17): 100% of these TH-LI neurons displayed NKR-like immunoreactivity, and they constituted about 3.5% of total NKR-LI neurons. The majority of double-labeled neurons with TH- and NKR-like immunoreactivities were distributed in the proximal inner nuclear layer and the upper part of inner plexiform layer of the retina, and characterized with appearance of amacrine cells. The present study has provided morphological evidence for direct physiological modulation of dopaminergic neurons by tachykinins through NKR in the rat retina (A17).
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PMID:Retinal dopaminergic neurons (A17) expressing neuromedin K receptor (NK(3)): a double immunocytochemical study in the rat. 1112 38

The neurokinin 3 (NK3) receptor is a novel target under investigation for improvement of symptoms of schizophrenia, because of its ability to modulate dopaminergic signaling. To further understanding of the function of this receptor, sensitivity to dopaminergic stimuli and levels of dopaminergic receptors and tyrosine hydroxylase in NK3 receptor knockout mice were studied. Knockout of the receptor was confirmed by lack of NK3 protein and lack of electrophysiological responsivity of presumed dopaminergic neurons to senktide. NK3 receptor knockout mice showed mild hyperlocomotion and deficits on the rotarod. NK3 receptor knockout mice did not show significant differences in sensitivity to locomotor effects of acute amphetamine (0.3, 1, and 3 mg/kg subcutaneously) or significant alterations in sensitization to locomotor effects of amphetamine, but did show nonsignificant hyperreactivity to 1 mg/kg amphetamine and a nonsignificantly increased propensity to develop sensitization. A small decrease in D1 receptor binding was seen in the dorsal striatum and olfactory tubercle, and a small decrease of in tyrosine hydroxylase in the olfactory tubercle, but no change was seen in D2 receptor binding. Together, these results support a role for the NK3 receptor in reactivity to dopaminergic stimuli, but the lack of robust changes indicates that the sensitivity to dopamine may be activity-dependent or benign in nature.
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PMID:Characterization of behavioral response to amphetamine, tyrosine hydroxylase levels, and dopamine receptor levels in neurokinin 3 receptor knockout mice. 1869 Jan 6

Neurokinin 3 (NK3) receptor is predominantly expressed in striatum and substantia nigra (SN). Evidences have indicated the roles of NK3 receptor in the pathogenesis of Parkinson's disease. By administrating NK3 receptor agonist senktide into 6-hydroxydopamine (6-OHDA)-lesioned rats, exacerbation of dopaminergic degeneration was found in striatum and substantia nigra pars compacta. From apomorphine rotation test, significant increase of contralateral rotation number was detected in 6-OHDA-lesioned rats with senktide injection. Furthermore, tyrosine hydroxylase expression in striatum and substantia nigra pars compacta were examined by immunohistochemistry and Western blotting. Further reduction of tyrosine hydroxylase immunoreactivities was found in 6-OHDA-lesioned rats that received senktide treatment. Also, phosphorylation of N-methyl-D-aspartate receptor 1 subunit was investigated in SN region and significant up-regulation was revealed in senktide-treated 6-OHDA-lesioned rats. Finally, phosphorylation of mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) and c-Jun were examined in nigral region. Up-regulation of phosphorylated JNK molecules was shown in SN region after senktide injection. In line with this evidence, phosphorylation of c-Jun at Ser 63 and Ser 73 was also up-regulated by senktide treatment, thus presenting new aspects that NK3 peptide could exacerbate 6-OHDA toxicity in in vivo models and the possible mechanism may be contributed by the modulation of N-methyl-D-aspartate receptor 1 subunit and JNK pathway activities.
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PMID:Neurokinin receptor 3 peptide exacerbates 6-hydroxydopamine-induced dopaminergic degeneration in rats through JNK pathway. 2276 52