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)

Adrenomedullin (AM) is a novel neuropeptide with special significance in the mammalian hypothalamo-hypophysial axis. By using an antiserum specific for human AM, we have studied the localization of AM-like immunoreactive (AMi) cell bodies and fibers in the hypothalamus and hypophysis of the amphibians Rana perezi (anuran), Pleurodeles waltl (urodele), and Dermophis mexicanus (gymnophionan). Distinct AMi cell groups were found for each species. In the anuran, six cell groups were localized in the preoptic and infundibular regions, whereas only three and one were found in the urodele and gymnophionan, respectively. A comparative analysis of AMi cells and cells expressing arginine vasotocin (AVT), neuropeptide Y (NPY), and tyrosine hydroxylase (TH) revealed strong differences between species. Thus, colocalization of AVT/AM is most likely to occur in the preoptic magnocellular nucleus of urodeles and it is reflected by the intense AM immunoreactivity in the neural lobe of the hypophysis. Colocalization of NPY/AM seems to be possible in the suprachiasmatic nucleus of anurans. In the gymnophionan, cells containing AVT and NPY are distinct from AMi cells. Only in anurans, the ventral aspect of the suprachiasmatic nucleus possesses a small population of AMi cells that express also TH immunoreactivity and most likely also express NPY. The results strongly suggest that AM in amphibians plays an important regulatory role in the hypothalamo-hypophysial system, as has been demonstrated in mammals. On the other hand, substantial differences have been found between species with respect to the degree of colocalization with other chemical substances.
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PMID:Comparative analysis of adrenomedullin-like immunoreactivity in the hypothalamus of amphibians. 1145

The goal of this study was to determine the immunohistochemical characteristics of peripheral adrenergic OBR-immunoreactive (OBR-IR) neurons innervating adipose tissue in a pig. The retrograde tracer, Fast Blue (FB), was injected into either the subcutaneous, perirenal, or mesentery fat tissue depots of three male and three female pigs each with approximately 50 kg body weight. Sections containing FB(+) neurons were stained for OBR, tyrosine hydroxylase (TH) or neuropeptide Y (NPY) using a double labeling immunofluorescence method. OBR, TH, and NPY immunoreactivities were present in the thoracic (T) and lumbar (L) ganglia of the sympathetic chain, as well as in the coeliac superior mesenteric ganglion (CSMG), inferior mesenteric ganglion (IMG), intermesenteric ganglia (adrenal-ADG, aorticorenal-ARG, and ovarian-OG or testicular-TG ganglion). These results indicate that, in addition to neuroendocrine functions, leptin may affect peripheral tissues by acting on receptors located in sympathetic ganglion neurons.
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PMID:Leptin receptors, NPY, and tyrosine hydroxylase in autonomic neurons supplying fat depots in a pig. 1205 78

The aim of the present study was to gain information about adrenergic-, cholinergic- and non-adrenergic, non-cholinergic (NANC)- transmitter systems/mediators in the rat vagina, and to characterize its smooth muscles functionally. Tissue sections from vagina of Sprague Dawley rats were immunolabelled with antibodies against protein gene product 9.5 (PGP), synaptophysin (Syn), tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), neuropeptide Y (NPY), nitric oxide synthase (NOS), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Circularly cut vaginal smooth muscle preparations from the distal vagina were studied in organ baths. In the paravaginal tissue, a large number of PGP-, NOS-, TH-, VIP-immunoreactive (IR) and few CGRP-IR nerve trunks were observed, giving off branches to the smooth muscle wall. The smooth muscle wall was supplied by a large number of PGP-, Syn-, VAChT-, NPY-, NOS- and TH- IR nerve terminals, whilst only a moderate to few numbers of CGRP-, VIP- and PACAP-IR terminals were identified. Especially the distal part of the vaginal wall, where the circularly running smooth muscle was thickened into a distinct sphincter structure, was very richly innervated, predominantly by PGP- and NOS-IR terminals. Below and within the basal parts of the epithelium in the distal half of the vagina, a large number of PGP- and few NOS- and PACAP-IR varicose terminals were observed. The vaginal arteries were encircled by plexuses of nerve terminals. A large number of these were PGP-, Syn-, VAChT-, NOS-, TH-, NPY- and VIP-IR, and few were CGRP- and PACAP-IR. In isolated preparations of the distal vagina, electrical field stimulation (EFS) caused frequency-dependent contractions, which were reduced by sildenafil, tetrodotoxin (TTX) and phentolamine. In preparations contracted by norepinephrine (NA), EFS produced frequency-dependent relaxations. Pretreatment with the NOS-inhibitor N(G)-nitro-L-arginine, TTX, or the inhibitor of soluble guanylate cyclase, ODQ, abolished the EFS relaxations. In NE precontracted preparations, cumulative addition of sildenafil caused concentration-dependent relaxation. Carbachol contracted the strips concentration-dependently from baseline. It can be concluded that the distal part of the rat vagina forms a distinct smooth muscle sphincter, which is richly innervated by adrenergic, cholinergic and NANC nerves. The present studies suggest that in the rat the L-arginine/NO-system not only plays an important role in the regulation of vaginal smooth muscle tone, but also affects blood flow, and may have sensory functions.
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PMID:Morphological and functional characterization of a rat vaginal smooth muscle sphincter. 1215 17

Hodological, electrophysiological, and ablation studies indicate a role for the basal forebrain in telencephalic vocal control; however, to date the organization of the basal forebrain has not been extensively studied in any nonmammal or nonhuman vocal learning species. To this end the chemical anatomy of the avian basal forebrain was investigated in a vocal learning parrot, the budgerigar (Melopsittacus undulatus). Immunological and histological stains, including choline acetyltransferase, acetylcholinesterase, tyrosine hydroxylase, dopamine and cAMP-regulated phosphoprotein (DARPP)-32, the calcium binding proteins calbindin D-28k and parvalbumin, calcitonin gene-related peptide, iron, substance P, methionine enkephalin, nicotinamide adenine dinucleotide phosphotase diaphorase, and arginine vasotocin were used in the present study. We conclude that the ventral paleostriatum (cf. Kitt and Brauth [1981] Neuroscience 6:1551-1566) and adjacent archistriatal regions can be subdivided into several distinct subareas that are chemically comparable to mammalian basal forebrain structures. The nucleus accumbens is histochemically separable into core and shell regions. The nucleus taeniae (TN) is theorized to be homologous to the medial amygdaloid nucleus. The archistriatum pars ventrolateralis (Avl; comparable to the pigeon archistriatum pars dorsalis) is theorized to be a possible homologue of the central amygdaloid nucleus. The TN and Avl are histochemically continuous with the medial aspects of the bed nucleus of the stria terminalis and the ventromedial striatum, forming an avian analogue of the extended amygdala. The apparent counterpart in budgerigars of the mammalian nucleus basalis of Meynert consists of a field of cholinergic neurons spanning the basal forebrain. The budgerigar septal region is theorized to be homologous as a field to the mammalian septum. Our results are discussed with regard to both the evolution of the basal forebrain and its role in vocal learning processes.
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PMID:Organization of the avian basal forebrain: chemical anatomy in the parrot (Melopsittacus undulatus). 1245 5

The purpose of this study was to examine cardiovascular responses to fourth cerebral ventricle (4V) administration of nitroglycerin (NTG) or an inhibitor of nitric oxide (NO) synthase (NOS) in the near-term ovine and to determine whether, during birth, neuronal NOS (nNOS) is induced in noradrenergic A1 neurons in the medial nucleus tractus solitarius (mNTS). In chronically instrumented fetal sheep, 4V injection of NTG (1.2 nmol), an NO donor, produced an arterial blood depressor and a moderate decrease in heart rate. Arterial blood pressure is increased by 4V administration of NG-nitro-L-arginine methyl ester (10 nmnol), an inhibitor of NOS, in fetuses. Sections of the medulla from fetuses and newborn lambs were examined by using immunolabeling with tyrosine hydroxylase (TH) antibody combined with NADPH diaphorase (NADPHd) histochemistry, a marker of nNOS activity. The NADPHd-positive cells and TH-positive cells containing NADPHd reactivity were significantly increased in the mNTS of newborns compared with the fetuses. The results suggest that during birth, there is upregulation of NADPHd/nNOS in the noradrenergic neurons of mNTS resulting in a centrally mediated reduction of fetal arterial blood pressure.
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PMID:Cardiovascular regulation and expressions of NO synthase-tyrosine hydroxylase in nucleus tractus solitarius of ovine fetus. 1266 63

Activation of esophageal mechanosensors excites neurons in and near the central nucleus of the solitary tract (NSTc). In turn, NSTc neurons coordinate the relaxation of the stomach [i.e., the receptive relaxation reflex (RRR)] by modulating the output of vagal efferent neurons of the dorsal motor nucleus of the vagus (DMN). The NSTc area contains neurons with diverse neurochemical phenotypes, including a large population of catecholaminergic and nitrergic neurons. The aim of the present study was to determine whether either one of these prominent neuronal phenotypes was involved in the RRR. Immunohistochemical techniques revealed that repetitive esophageal distension caused 53% of tyrosine hydroxylase-immunoreactive (TH-ir) neurons to colocalize c-Fos in the NSTc. No nitric oxide synthase (NOS)-ir neurons in the NSTc colocalized c-Fos in either distension or control conditions. Local brain stem application (2 ng) of alpha-adrenoreceptor antagonists (i.e., alpha1-prazosin or alpha2-yohimbine) significantly reduced the magnitude of the esophageal distension-induced gastric relaxation to approximately 55% of control conditions. The combination of yohimbine and prazosin reduced the magnitude of the reflex to approximately 27% of control. In contrast, pretreatment with either the NOS-inhibitor NG-nitro-l-arginine methyl ester or the beta-adrenoceptor antagonist propranolol did not interfere with esophageal distension-induced gastric relaxation. Unilateral microinjections of the agonist norepinephrine (0.3 ng) directed at the DMN were sufficient to mimic the transient esophageal-gastric reflex. Our data suggest that noradrenergic, but not nitrergic, neurons of the NSTc play a prominent role in the modulation of the RRR through action on alpha1- and alpha2-adrenoreceptors. The finding that esophageal afferent stimulation alone is not sufficient to activate NOS-positive neurons in the NSTc suggests that these neurons may be strongly gated by other central nervous system inputs, perhaps related to the coordination of swallowing or emesis with respiration.
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PMID:Noradrenergic neurons in the rat solitary nucleus participate in the esophageal-gastric relaxation reflex. 1271 55

The present study examined whether thrombin-induced microglial activation could contribute to death of dopaminergic neurons in the rat substantia nigra (SN) in vivo. Seven days after thrombin injection into the SN, tyrosine hydroxylase immunohistochemistry showed a significant loss of nigral dopaminergic neurons. In parallel, thrombin-activated microglia, visualized by immunohistochemical staining using antibodies against the complement receptor type 3 (OX-42) and the major histocompatibility complex class II antigens were also observed in the SN, where degeneration of nigral neurons was found. Reverse transcription PCR at various time points demonstrated that activated microglia in vivo exhibited an early and transient expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and several proinflammatory cytokines, including interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor alpha. Western blot analysis and double-label immunohistochemistry showed an increase in the expression of iNOS and COX-2 and the colocalization of these proteins within microglia. The thrombin-induced loss of SN dopaminergic neurons was partially inhibited by NG-nitro-L-arginine methyl ester hydrochloride, an NOS inhibitor, and by DuP-697, a COX-2 inhibitor. Additional studies demonstrated that extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) were activated in the SN as early as 30 min after thrombin injection, and that these kinases were localized within microglia. Inhibition of ERK1/2 and p38 MAPK reduced iNOS and COX-2 mRNA expression and rescued dopaminergic neurons in the SN. The present results strongly suggest that microglial activation triggered by endogenous compound(s) such as thrombin may be involved in the neuropathological processes of dopaminergic neuronal cell death that occur in Parkinson's disease.
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PMID:Thrombin-induced microglial activation produces degeneration of nigral dopaminergic neurons in vivo. 1284 92

Nitric oxide (NO), in excess, behaves as a cytotoxic substance mediating the pathological processes that cause neurodegeneration. The NO-induced dopaminergic cell loss causing Parkinson's disease (PD) has been postulated to include the following: an inhibition of cytochrome oxidase, ribonucleotide reductase, mitochondrial complexes I, II, and IV in the respiratory chain, superoxide dismutase, glyceraldehyde-3-phosphate dehydrogenase; activation or initiation of DNA strand breakage, poly(ADP-ribose) synthase, lipid peroxidation, and protein oxidation; release of iron; and increased generation of toxic radicals such as hydroxyl radicals and peroxynitrite. NO is formed by the conversion of L-arginine to L-citrulline by NO synthase (NOS). At least three NOS isoforms have been identified by molecular cloning and biochemical studies: a neuronal NOS or type 1 NOS (nNOS), an immunologic NOS or type 2 NOS (iNOS), and an endothelial NOS or type 3 NOS (eNOS). The enzymatic activities of eNOS or nNOS are induced by phosphorylation triggered by Ca(2+) entering cells and binding to calmodulin. In contrast, the regulation of iNOS seems to depend on de novo synthesis of the enzyme in response to a variety of cytokines, such as interferon-gamma and lipopolysaccharide. The evidence that NO is associated with neurotoxic processes underlying PD comes from studies using experimental models of this disease NOS inhibitors can prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity. Furthermore, NO fosters dopamine depletion, and the said neurotoxicity is averted by nNOS inhibitors such as 7-nitroindazole working on tyrosine hydroxylase-immunoreactive neurons in substantia nigra pars compacta. Moreover, mutant mice lacking the nNOS gene are more resistant to MPTP neurotoxicity when compared with wild-type littermates. Selegiline, an irreversible inhibitor of monoamine oxidase B, is used in PD as a dopaminergic function-enhancing substance. Selegiline and its metabolite, desmethylselegiline, reduce apoptosis by altering the expression of a number of genes, for instance, superoxide dismutase, Bcl-2, Bcl-xl, NOS, c-Jun, and nicotinamide adenine nucleotide dehydrogenase. The selegiline-induced antiapoptotic activity is associated with prevention of a progressive reduction of mitochondrial membrane potential in preapoptotic neurons. As apoptosis is critical to the progression of neurodegenerative disease, including PD, selegiline or selegiline-like compounds to be discovered in the future may be efficacious in treating PD.
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PMID:Peroxynitrite and mitochondrial dysfunction in the pathogenesis of Parkinson's disease. 1288 Apr 86

There is a long-known hyper-responsiveness of vascular adrenergic transmission in the spontaneously hypertensive rat (SHR) that is uncovered specifically in the presence of cocaine and attributed to blockade of the neuronal monoamine transporter. We have now used the rat anococcygeus muscle to investigate whether this phenomenon is generic to sympathetic transmission to smooth muscle rather than a purely vascular phenomenon. We sought the origin of the effect by successively blocking the buffering effects of the neuronal monoamine transporter, prejunctional alpha2-adrenoceptors and NO from nitrergic nerves with desipramine (0.1 microm), rauwolscine (0.01 microm) and l-NG-nitro-arginine (100 microm). In the presence of desipramine, contractile responses to electrical field stimulation but not to noradrenaline (1 nm-100 microm) were greater in SHR than in Wistar-Kyoto (WKY). Neither inhibition of prejunctional alpha2-adrenoceptors nor the blockade of neuronal nitric oxide synthase (nNOS) accounted for the differential enhancement of response in SHR. The enhanced effectiveness of motor neurotransmission in SHR becomes most apparent when all known major buffering mechanisms are removed. When nitrergic responses were isolated pharmacologically (phentolamine 1 microm and guanethidine 30 microm; tone raised with carbachol 50 microm), they were not different between SHR and WKY. Western blots showed that both nNOS and tyrosine hydroxylase are expressed to a similar extent in anococcygeus muscle from SHR and WKY, suggesting similar adrenergic and nitrergic innervations in the two strains. This suggests that enhanced motor transmission is due to increased transmitter release per varicosity rather than there being normal transmission from a greater number of sites. We conclude that there is a generic enhancement of sympathetic transmission in SHR rather than this being a vascular phenomenon.
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PMID:Enhanced noradrenergic transmission in the spontaneously hypertensive rat anococcygeus muscle. 1450 40

Nurr1 is a transcription factor essential for the development of ventral dopaminergic neurons. In search for regulatory mechanisms of Nurr1 function, we identified the SUMO (small ubiquitin-like modifier)-E3 ubiquitin-protein isopeptide ligase, PIASgamma, as an interaction partner of Nurr1. Overexpressed PIASgamma and Nurr1 co-localize in the nuclei of transfected cells, and their interaction is demonstrated through co-immunoprecipitation and glutathione S-transferase pulldown assays. Co-expression of PIASgamma with Nurr1 results in a potent repression of Nurr1-dependent transcriptional activation of an artificial NGFI-B response element (NBRE) reporter as well as of a reporter driven by the native tyrosine hydroxylase promoter. We identified two consensus sumoylation sites in Nurr1. The substitution of lysine 91 by arginine in one SUMO site enhanced the transcriptional activity of Nurr1, whereas the substitution of lysine 577 by arginine in the second SUMO site decreased transcriptional activity of Nurr1. Interestingly, PIASgamma-induced repression of Nurr1 activity does not require the two sumoylation sites, because each mutant is repressed as efficiently as the wild type Nurr1. In addition, the mutations do not alter Nurr1 nuclear localization. Finally, we provide evidence that Nurr1 and PIASgamma co-exist in several nuclei of the rodent central nervous system by demonstrating the co-expression of Nurr1 protein and PIASgamma mRNA in the same cells. In conclusion, our studies identified PIASgamma as a transcriptional co-regulator of Nurr1 and suggest that this interaction may have a physiological role in regulating the expression of Nurr1 target genes.
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PMID:PIASgamma represses the transcriptional activation induced by the nuclear receptor Nurr1. 1455 18


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