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)

beta-Adrenergic receptors (beta AR) in the medial nuclei of tractus solitarii (m-NTS) and area postrema (AP) may bind to catecholamines released from neurons, whereas only the AP has fenestrated capillaries allowing access to circulating catecholamines. Since varied autonomic responses are seen following beta AR activation of the dorsal vagal complex, including the m-NTS and AP, we hypothesized that there might be a cellular basis for varied responses to beta AR stimulation that depends on the differential access to circulating catecholamines. Therefore, we comparatively examined the ultrastructural localization of the beta AR in relation to catecholaminergic neurons in these regions. An antibody directed against the C-terminal tail (amino acids 404-418) of hamster beta-adrenergic receptor (beta AR404) was used in this study. The localization of beta AR404 was achieved by the avidin-biotin peroxidase complex (ABC) technique in combination with a pre-embed immunogold labeling method to localize tyrosine hydroxylase (TH), the catecholamine-synthesizing enzyme. Within m-NTS and at subpostremal border, labeling for beta AR404 was evident along the intracellular surface of plasma membranes of small, apparently distal, astrocytic processes. Astrocytic processes with beta AR404-immunoreactivity formed multiple, thin lamellae around TH-labeled and non-TH neuronal cell bodies and dendrites. beta AR404-immunoreactive astrocytes also extended end-feet around blood vessels and surrounded groups of axon terminals that were directly juxtaposed to each other. Some, but not all, of these axons demonstrated TH-immunoreactivity. Fewer beta AR404-immunoreactive astrocytes were detected in AP, regardless of their proximity to catecholaminergic processes or blood vessels. The present astrocytic localization of beta AR404, together with the earlier, neuronal localization of beta AR's third intracellular loop, suggest that the beta AR may be substantially different between neurons and astrocytes. The regional difference in the prevalence of beta AR404-immunoreactive astrocytes suggests that these receptive sites may either: (i) be preferentially activated by catecholamines released from terminals rather than circulating catecholamines; or (ii) be down-regulated in AP due to blood-born substances, such as catecholamines. The extensive localization of beta AR in the border between m-NTS and AP also suggests that catecholaminergic activation of these astrocytes may dictate the degree of diffusion of catecholamines which are of neuronal or vascular origin. The specific localization of beta AR404-immunoreactivity to the more distal portions of astrocytes suggests the possibility that astrocytes have restrictive distributions of beta AR and that the beta-adrenergic activation lead to morphological or chemical changes that are also localized to the distal portions of astrocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:C-terminal tail of beta-adrenergic receptors: immunocytochemical localization within astrocytes and their relation to catecholaminergic neurons in N. tractus solitarii and area postrema. 135 76

Alpha 2-adrenergic binding sites in the medulla oblongata of tree shrews and rats were detected and quantified by in vitro-autoradiography with the alpha 2-antagonist 3H-rauwolscine (3H-RAUW). The autoradiographic pattern of the radioligand binding in the tree shrew medulla oblongata resembles that which has been described by others for the human myelencephalon. This pattern coincides well with the occurrence of catecholaminergic structures detected by immunocytochemistry with antibodies against phenylethanolamine-N-methyltransferase and tyrosine hydroxylase. In contrast to the rat, where only the nucleus tractus solitarii and the nucleus dorsalis nervi vagi were labeled, five discrete nuclei specifically bound 3H-RAUW in tree shrews. The highest number of binding sites was detected in the nucleus dorsalis nervi vagi (nX; Bmax: 333 fmoles/mg) and the nucleus tractus solitarii (NTS; 311 fmoles/mg), followed by the nucleus nervi hypoglossi (nXII; 297 fmoles/mg), the nucleus reticularis parvocellularis (FRS; 230 fmoles/mg), and the area of the catecholamine cell groups A1 and C1 (area C1; 202 fmoles/mg). Maximal binding in the two labeled nuclei of the rat was 158 fmoles/mg. The discrete nuclei of the two species also showed different affinities for 3H-RAUW with Kd ranging from 0.17 to 0.83 nM in tree shrews and 1.80 to 1.95 nM in rats. Competition experiments revealed that the radioligand bound specifically to alpha 2-binding sites. In the tree shrew, nX, nXII and the area C1, also have a relatively high affinity for the alpha 1-antagonist prazosin which is a quality of the adrenoceptor subtype alpha 2B. Furthermore, in the area C1, 3H-RAUW binding was inhibited by the dopamine antagonist haloperidol. There are thus species related as well as regional differences with respect to the number, the affinity, and the pharmacological properties of alpha 2-binding sites in the medulla oblongata. In tree shrews, alpha 2-adrenoceptors can be autoradiographically quantified in regions which are not labeled in the rat, although former data predicted the existence of such receptors, e.g., in the area of the adrenaline cell group C1.
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PMID:Alpha 2-adrenergic binding sites in the medulla oblongata of tree shrews demonstrated by in vitro autoradiography: species related differences in comparison to the rat. 197 22

Interactions between central opioids and catecholamines are thought to underlie the ability of adrenergic agonists both to lower blood pressure and alleviate certain symptoms of opiate withdrawal. We examined the cellular substrate for interactions between neurons containing enkephalin-like opioid peptides and catecholamines in cardiovascular portions of the medial nuclei of the solitary tracts (m-NTS) of adult rats. Single sections were dually labeled using a double-bridged peroxidase method for the localization of a monoclonal leucine (Leu5)-enkephalin-antibody and immunoautoradiography for the localization of polyclonal antibodies against the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH). Light microscopy revealed a few perikarya and numerous varicosities containing Leu5-enkephalin-like immunoreactivity (LE-LI). These were distributed among TH-labeled perikarya and processes throughout the rostrocaudal NTS. Electron microscopy of the m-NTS at the level of the area postrema further established the single as well as dual localization of TH and LE-LI in individual perikarya, dendrites, and axon terminals. Silver grains indicative of TH-labeling were usually distributed throughout the cytoplasm, whereas the peroxidase reaction product for LE-LI was localized principally to large (80-150 nm), dense-core vesicles. Immunoautoradiographic labeling for TH was detected in 118 terminals within a series of sections containing 183 terminals with LE-LI. Of these, 26% of the TH-labeled terminals and 32% of the enkephalin-containing terminals formed symmetric synapses with unlabeled dendrites, while only 7% of each type formed symmetric synapses with TH-labeled dendrites. In favorable planes of sections, the unlabeled as well as TH-labeled dendrites received convergent input from both types of terminals. A few of the remaining terminals that contained either TH or LE-LI formed asymmetric junctions with unlabeled distal dendrites; the others were without recognizable synaptic specializations within the plane of section. Approximately 20% of the TH-labeled terminals and 6% of the terminals containing LE-LI were dually labeled for both antibodies. These were invested with astrocytic processes characterized by bundles of intermediate filaments. We conclude that within cardiovascular portions of the m-NTS, opioid peptides and catecholamines contained within the same or separate terminals modulate the activity of target neurons through direct symmetric, probably inhibitory, synaptic junctions and may additionally modulate the activity of neighboring astrocytes through exocytotic release from large dense-core vesicles.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ultrastructural basis for interactions between central opioids and catecholamines. II. Nuclei of the solitary tracts. 256 12

Pharmacological studies suggest that beta-adrenergic receptors (beta AR) in the medial nuclei of the solitary tracts (m-NTS) facilitate presynaptic release of catecholamines and also function at postsynaptic sites. We have localized the antigenic sites for a monoclonal antibody against a peptide corresponding to amino acids 226-239 of beta AR in the m-NTS of rat brain. By light microscopy, immunoperoxidase labeling for this antibody was detected in somata and proximal processes of many small cells that were distributed throughout the rostrocaudal extent of the m-NTS. Electron microscopy confirmed the cytoplasmic localization of beta AR in perikarya and proximal dendrites of neurons. Immunoreactivity occurred as discrete patches associated with cytoplasmic surfaces of plasma membrane and with irregularly-shaped saccules with clear lumen in the immediate vicinity. Select regions of nuclear envelopes, mitochondrial membranes, and rough endoplasmic reticulum were also immunoreactive along their cytoplasmic surfaces. In contrast, the Golgi apparatus was labeled, but infrequently. Immunoreactivity was also detected at numerous post- and occasional presynaptic membrane specializations of select axodendritic junctions. Dual labeling for the beta AR-antibody by the immunoperoxidase method and for a rabbit antiserum against the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), by the immunoautoradiographic method within the same sections, further established the precise cellular relations between beta AR and catecholaminergic neurons. Immunoreactivity for beta AR was detected in numerous perikarya and proximal dendrites that did not show detectable levels of TH. However, a few cells were dually labeled for both antigens, as seen by both light and electron microscopy. The TH-labeled terminals formed synapses at junctions both with and without beta AR-like immunoreactivity. These results from the single and dual labeling studies: (1) confirm biochemical predictions that amino acids 226-239 of beta AR protein reside intracellularly; (2) provide the first ultrastructural evidence for beta AR localization within both pre- and postsynaptic membrane specializations of a subset of catecholaminergic synapses; and (3) suggest select intracellular sites that may be involved with synthesis and/or internalization and degradation of the receptor protein.
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PMID:Cytoplasmic loop of beta-adrenergic receptors: synaptic and intracellular localization and relation to catecholaminergic neurons in the nuclei of the solitary tracts. 256 14

The distribution of opiocortin- (OP-ir) and tyrosine hydroxylase-immunoreactive (TH-ir) perikarya was examined immunocytochemically in rats treated neonatally with the neurotoxin monosodium glutamate (MSG). While OP-ir and TH-ir perikarya were eliminated in the arcuate nucleus in treated animals, the OP-ir and TH-ir cell groups of the nucleus tractus solitarius and contiguous medullary regions were unaffected. This selective elimination of arcuate neurons permitted us to examine specifically the fiber projections of the medullary OP-ir perikarya in treated animals. This revealed a preferential distribution of delicate fibers originating in NTS, to discrete medullary and pontine areas. In control animals, these same terminal fields appeared to be more densely populated with an additional population of thicker OP-ir fibers, suggesting the possibility of a shared innervation of these brainstem regions by both hypothalamic and medullary OP-ir neurons.
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PMID:Differential sensitivity of hypothalamic and medullary opiocortin and tyrosine hydroxylase neurons to the neurotoxic effects of monosodium glutamate (MSG). 287 78

The ultrastructural morphology of serotoninergic terminals and their synaptic relation with catecholaminergic neurons were examined in the medial nuclei of the solitary tracts (m-NTS) using combined autoradiographic and immunocytochemical methods. Adult rats were pretreated with a monoamine oxidase inhibitor and subjected to a 2-hour intraventricular infusion of 50 nM tritiated 5-hydroxytryptamine (3H-5HT). At the termination of the infusion, the brains were fixed by aortic arch perfusion with a mixture of 4% paraformaldehyde and 0.5% glutaraldehyde. Coronal Vibratome sections through the NTS and more rostral raphe nuclei were immunocytochemically labeled with specific antiserum to serotonin or tyrosine hydroxylase and then processed for autoradiography. By light microscopy, concentrations of reduced silver grains indicating uptake of 3H-5HT usually paralleled the localization of peroxidase immunoreactivity for serotonin in neuronal perikarya of the rostral raphe nuclei and in varicosities in the brainstem. The 3H-5HT-containing varicosities were found throughout the medial and commissural portions of the NTS, where they were frequently associated with processes showing immunoreactivity for the catecholamine-synthesizing enzyme tyrosine hydroxylase. Ultrastructural examination of the m-NTS revealed that the silver grains for 3H-5HT were accumulated over axon terminals. The 5HT-labeled terminals contained a heterogeneous population of vesicles and formed both symmetric and asymmetric synapses with dendrites. The recipient dendrites were either, unlabeled or showed immunoreactivity for tyrosine hydroxylase. These findings support a direct serotoninergic modulation of catecholaminergic neurons within the rat m-NTS.
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PMID:Serotoninergic terminals: ultrastructure and synaptic interaction with catecholamine-containing neurons in the medial nuclei of the solitary tracts. 614 1

The immunocytochemical localizations of substance P, neurotensin, enkephalin and the catecholamine-synthesizing enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase were examined in the rat parabrachial region. The immunoreactivity for each marker was compared with the distribution of superimposed autoradiographic labeling of parabrachial afferents after unilateral injection of 3H-amino acids into the caudal portion of the medial nucleus of the solitary tract (m-NTS). Substance-P- and neurotensinlike immunoreactivity (SPLI and NTLI, respectively) were localized primarily in varicose processes in the ventrolateral quadrant of the parabrachial region. The SPLI and NTLI were differentially localized with respect to each other; however, both peptides were detected in regions of the parabrachial containing dense autoradiographic label. In contrast, enkephalinlike immunoreactivity (ELI), tyrosine hydroxylase, and dopamine-beta-hydroxylase were detected in processes and a few perikarya located outside the ventrolateral parabrachial region. The ELI was primarily in the dorsolateral, and the catecholamine-synthesizing enzymes were primarily in the medial parabrachial regions which contained sparse autoradiographic labeling of transported amino acids. We conclude that in the rat parabrachial region, SPLI and NTLI are contained within two distinct populations of afferents which may originate from perikarya in the caudal m-NTS, whereas ELI and the catecholamines are more likely to be found in other afferents or possibly in intrinsic neurons.
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PMID:Substance P, neurotensin, enkephalin, and catecholamine-synthesizing enzymes: light microscopic localizations compared with autoradiographic label in solitary efferents to the rat parabrachial region. 620 25

By using double immunolabeling light and electron microscopic techniques, dense neuronal network of calcitonin-related peptide (CGRP) has been visualized in the nucleus of the solitary tract with complete overlapping of the tyrosine hydroxylase (TH)-containing cells. TH-immunoreactive perikarya and dendrites were seen in synaptic contact with CGRP-immunopositive fibers, indicating that CGRP, by carrying sensory signals may influence autonomic regulatory mechanisms in the NTS through local catecholaminergic neurons.
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PMID:Calcitonin gene-related peptide innervation of A2-catecholamine cells in the nucleus of the solitary tract of the rat. 749 1

The primary baroreceptor area (nucleus of the solitary tract-NTS) is anatomically interconnected with the rostral ("vasomotor area") and the caudal ("vasodepressor area") ventrolateral medulla by a well-defined arc of neuronal pathways. The chemical character and the direction of these pathways have been investigated with immunohistochemical and neurochemical techniques in intact and brainstem-operated rats. The transection of the neuronal arc resulted in an accumulation of tyrosine hydroxylase immunoreactivity in a small group of cells in the NTS adjacent to the area postrema, ipsilateral to the knife cut. Decreased angiotensinogen mRNA and atrial natriuretic peptide concentrations were measured in the ventrolateral medulla after the cut, and an accumulation of angiotensin II-immunoreactivity was found in neuronal perikarya in the ipsilateral NTS. Intracranial vagotomy caused marked depletions in glutamate levels in the subcommissural portion of the NTS and in the caudal ventrolateral medulla but nowhere else in the brainstem investigated including the rostral ventrolateral medulla.
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PMID:Neurotransmitters and neuropeptides in the baroreceptor reflex arc: connections between the nucleus of the solitary tract and the ventrolateral medulla oblongata in the rat. 773 61

We sought to identify the brain areas that might contribute to the increased autonomic activity seen during morphine withdrawal by mapping neuronal expression of c-fos protein (Fos) and Fos-related antigens. Rats were implanted with morphine pellets or placebo pellets over a 5 day regimen and injected on day 6 with either saline or naltrexone (100 mg/kg). After a standard PAP immunocytochemical protocol, Fos-like immunoreactivity (Fos-LIR) was observed in medullary nuclei including the NTS (nucleus of the solitary tract), caudal (CVL) and rostral ventrolateral medulla (RVL). Although some Fos-LIR was seen in these areas in control rats (either morphine-implanted, saline injected, or placebo-implanted, saline or naltrexone injected), a significantly higher number of Fos-LIR-positive cells in NTS, CVL and RVL were seen after morphine withdrawal. Large numbers of Fos-like immunoreactive cells were also seen in the A5 area, the parabrachial nuclei of the pons and the locus coeruleus. Increased Fos-LIR was also detected in the paraventricular nucleus of the hypothalamus and the amygdala of morphine withdrawn rats. The Fos-LIR was co-localized with tyrosine hydroxylase immunoreactivity in many of the cells in caudal and rostral ventrolateral medulla, A5 and locus coeruleus. These data support the conclusion that autonomic areas in brain and noradrenergic/adrenergic cells in these areas are activated during morphine withdrawal and may contribute to the autonomic symptoms of opiate withdrawal.
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PMID:Autonomic areas of rat brain exhibit increased Fos-like immunoreactivity during opiate withdrawal in rats. 790 68


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