Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta 2-Adrenergic receptor agonists inhibit the increase in vascular permeability produced by a variety of inflammatory mediators. The anti-edema effect of beta 2-agonists is assumed to result from a direct action on endothelial cells, but such a mechanism has not been demonstrated in vivo. The aim of this study was to determine whether beta 2-agonists exert their anti-edema effect by inhibiting the formation of endothelial gaps at sites of plasma leakage. Vascular permeability in the rat trachea was increased by electrical stimulation of the vagus nerve or by intravenous injection of substance P (5 micrograms/kg iv). Plasma leakage was quantified by using Monastral blue and Evans blue as tracers. Endothelial gaps were made visible for light microscopy by staining the borders of endothelial cells with silver nitrate. The experiments showed that the selective beta 2-agonist formoterol, which is known to have anti-edema effects, reduced the plasma leakage produced by either stimulus. The effect was dose dependent, with a formoterol dose of 10 micrograms/kg iv producing maximal reduction of Monastral blue leakage (64 +/- 14%). The amounts of extravasation of Monastral blue and Evans blue were closely correlated (r2 = 0.76, P < 0.01). After the injection of substance P, there were 15.3 +/- 1.0 gaps/endothelial cells in postcapillary venules of vehicle-pretreated rats, but only 5.0 +/- 0.2 gaps/cell in formoterol-pretreated (10 micrograms/kg iv) rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The beta 2-adrenergic receptor agonist formoterol reduces microvascular leakage by inhibiting endothelial gap formation. 751 64

Anatomical relationships between tachykinin-containing terminals and neurons of the medial preoptic area that innervate the arcuate nucleus were studied using silver staining of the retrograde tracer wheat germ agglutinin-apoperoxidase-gold (WGA-ApoHRP-gold) complex injected in the arcuate nucleus and pre-embedding immunocytochemistry for neurokinin A (NKA). At the histological level, retrogradely labeled cells not stained for NKA were seen to be surrounded by numerous NKA-immunopositive punctate profiles, in particular in the dorsal part of the medial preoptic area. At the ultrastructural level, retrogradely labeled cell bodies and dendritic profiles displayed highly electron-dense silver particle accumulations over the cytoplasm. The were seen in synaptic contact with one or several NKA-immunoreactive axon terminals containing small clear vesicles and dense-cored vesicles. Such synapses were either symmetrical or asymmetrical. The occurrence of synaptic contacts between tachykinin terminals and cells innervating the arcuate nucleus in the medial preoptic region provides a morphological support for a tachykinergic regulation of preoptic afferences to the arcuate nucleus. These results suggest that tachykinins are implicated in the indirect control of neuronal activity in the arcuate nucleus notably via the preoptic area. Consequently, tachykinins are potentially able to regulate indirectly numerous neuroendocrine events involving the tuberoinfundibular system.
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PMID:Tachykinergic synaptic inputs to neurons of the medial preoptic region which project to the rat arcuate nucleus. 751 35

The endogenous opioid peptide dynorphin is enriched in neurons in the nucleus accumbens, for which coexistence and synaptic interactions with substance P have been postulated. We examined the immunogold-silver localization of dynorphin and immunoperoxidase labeling for substance P in single coronal sections through the core subregion of the nucleus accumbens of acrolein-fixed rat brain tissue. Dynorphin-immunoreactive somata were more prevalent than substance P-containing neurons throughout the region sampled for ultrastructural analysis. Dynorphin-labeled cells were spherical, contained unindented nuclei, and were closely apposed to other somata and dendrites, some of which also contained dynorphin immunoreactivity. The appositions were characterized by the absence of glial processes and contiguous contacts between the plasma membranes. Smooth endoplasmic reticulum and coated vesicles could also be identified in the cytoplasms on either side of the somatic or dendritic appositions. The dynorphin somata and dendrites received synaptic input from numerous unlabeled as well as dynorphin- and/or substance P-labeled axon terminals. Both types of terminals were morphologically similar in their content of small and large dense core vesicles and their formation of mainly symmetric synaptic specializations. In addition to dynorphin-immunoreactive targets, numerous dynorphin- and substance P-labeled terminals also formed synapses with unlabeled somata and dendrites. In some cases, terminals separately labeled for dynorphin and substance P converged on common targets with or without detectable dynorphin immunoreactivity. Terminals colocalizing both peptides were also found to synapse on unlabeled or dynorphin-labeled somata and dendrites. Additionally, presynaptic interactions were suggested by close appositions between dynorphin- and/or substance P-labeled terminals and other terminals that were unlabeled, dynorphin labeled, or substance P labeled. These results provide morphological data suggesting nonsynaptic communication between dynorphin-immunoreactive neurons and other neurons possibly mediated through receptive sites or second messengers associated with smooth endoplasmic reticulum in the nucleus accumbens. They also indicate that, in this region, 1) the activity of dynorphin neurons may be dependent on activation of autoreceptors for dynorphin as well as substance P and 2) additional neurons lacking dynorphin immunoreactivity are most likely inhibited (symmetric junctions) by terminals containing either one or both peptides. The findings may have implications for motor and analgesic responses to aversive tonic pain transmitted through dynorphin and substance P pathways within the nucleus accumbens.
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PMID:Dynorphin-immunoreactive neurons in the rat nucleus accumbens: ultrastructure and synaptic input from terminals containing substance P and/or dynorphin. 753 73

The century-old histological technique of silver nitrate staining has proven to be extremely useful for visualizing endothelial cell borders and localizing endothelial gaps, but the significance of the staining is still not fully understood. To gain some insight into what silver nitrate stains, we developed a method that enabled us to use scanning electron microscopy with backscattered and secondary electron imaging to examine silver staining at endothelial cell borders of venules of the rat tracheal mucosa. We found that in normal venules, silver lines followed the smooth contour of cell borders. However, 1 min after endothelial permeability was increased by substance P, cell borders were irregular and displaced from the silver lines by as much as 4.3 microns, and the lines were accompanied by three types of silver deposits. Most common (46% of total) were annulus-shaped silver deposits that surrounded endothelial gaps. These deposits averaged 1.5 microns in width, were positioned symmetrically across cell borders, and were located at a depth of 0.3 micron beneath the luminal surface. Many endothelial gaps were partitioned into multiple pores (mean, 2.4) by fingerlike processes of endothelial cells. Surprisingly, the gaps occupied only 5.4% of the total area of the silver deposits and constituted 0.15% of the luminal surface of the leaky postcapillary venules. A second type of silver deposit (19% of total) was positioned asymmetrically with respect to the cell border and marked sites where endothelial cell margins still overlapped but appeared to be vertically separated by obliquely oriented gaps. A third type marked gaps at three-cell junctions; these were no more abundant than deposits elsewhere around the cell perimeter, suggesting that three-cell junctions were not unusually leaky sites. We conclude that silver nitrate marks endothelial cell borders and outlines endothelial cell gaps by staining an element of intercellular junctions. The annular shape of many silver deposits around gaps suggests that junctional elements in the apposing cells are separated during gap formation but are still present at the gap perimeter.
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PMID:Location of focal silver staining at endothelial gaps in inflamed venules examined by scanning electron microscopy. 757 75

Electron microscopic immunohistochemical double-label studies were carried out in pigeons to characterize the ultrastructural organization and postsynaptic targets of enkephalinergic (ENK+) striatonigral projection. ENK+ terminals in the substantia nigra were labeled with antileucine-enkephalin antiserum by using peroxidase-antiperoxidase methods, and dopaminergic neurons were labeled with anti-tyrosine hydroxylase antiserum by using silver-intensified immunogold methods. ENK+ terminals on dopaminergic neurons were equal in abundance to ENK+ terminals on nondopaminergic neurons, although the former were typically somewhat smaller than the latter (mean size: 0.50 vs. 0.75 micron, respectively). ENK+ terminals were evenly distributed on the cell bodies and dendrites of dopaminergic neurons, and they were evenly distributed on dendrites but rare on perikarya of nondopaminergic neurons. Transection of the basal telencephalic output revealed that 75% of the nigral ENK+ terminals were of basal telencephalic origin. These telencephalic ENK+ terminals included over 80% of those smaller than 0.80 micron on dopaminergic neurons and smaller than 1.0 micron on nondopaminergic neurons, and none greater than this in size. Both telencephalic and the nontelencephalic ENK+ nigral terminals made predominantly symmetric synapses on nigral neurons. Although the basal telencephalic ENK+ terminals uniformly targeted dendrites and perikarya, nontelencephalic ENK+ terminals seemed to avoid perikarya. The results indicate that ENK+ striatonigral neurons in birds may directly influence both dopaminergic and nondopaminergic neurons of the substantia nigra. Based on similar data for substance P-containing striatonigral terminals, the roles of enkephalin and substance P in influencing nigral dopaminergic neurons may differ slightly, as they appear to target preferentially different portions of dopaminergic neurons. The overall results in pigeons are similar to those for ENK+ terminals in the ventral tegmental area in rats, suggesting that the synaptic organization of the ENK+ input to the tegmental dopaminergic cell fields is similar in mammals and birds.
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PMID:An ultrastructural double-label immunohistochemical study of the enkephalinergic input to dopaminergic neurons of the substantia nigra in pigeons. 767 76

The presence of neuropeptides in brainstem neurons that project to the medial and lateral thalamus and zona incerta has been studied in the rat. Brainstem neurons were retrogradely labeled from the medial and lateral thalamus and the zona incerta by colloidal gold-WGA-HRP and, after silver intensification of the retrograde label, their content of immunoreactivity for nine different neuropeptides was determined after colchicine administration. The medial thalamus and zona incerta both received a large peptidergic input and the lateral thalamus a smaller input from neurons in several brainstem nuclei. These were principally from the locus coeruleus, parabrachial nucleus, the dorsal raphe and the dorsal tegmentum. The principal input to the medial thalamus arose from neurotensin, neuropeptide Y and galanin neurons in the locus coeruleus, neurotensin neurons in the dorsal tegmentum, dynorphin neurons in the parabrachial nucleus and dorsal tegmentum, galanin neurons in the dorsal raphe, substance P neurons in the lateral and dorsal periaqueductal grey and calcitonin gene-related peptide neurons in the nucleus paragigantocellularis. The principal peptidergic input to the zona incerta was from dynorphin neurons in the nucleus of the solitary tract, bombesin neurons in the lateral reticular nucleus, calcitonin gene-related peptide and cholecystokinin neurons in the dorsal tegmentum, substance P, bombesin and galanin neurons in the locus coeruleus, dynorphin and substance P neurons in the lateral periaqueductal grey and cholecystokinin neurons in the substantia nigra, ventral tegmental nucleus and raphe linearis. The principal peptidergic input to the lateral thalamus came from calcitonin gene-related peptide and cholecystokinin neurons in the dorsal tegmentum, calcitonin gene-related peptide and galanin neurons in the locus coeruleus; substance P, neuropeptide Y, galanin and calcitonin gene-related peptide neurons in the dorsal raphe, substance P neurons in the lateral periaqueductal gray, galanin neurons in the nucleus interpedunculus and cholecystokinin neurons in the raphe linearis. In all these cases, from 25% to virtually all of the projection neurons in the brainstem nucleus could contain immunoreactivity to the neuropeptide. A lesser, but significant peptidergic input to the thalamus and zona incerta also arose from the trigeminal nucleus, the substantia nigra, the nucleus of the solitary tract, the lateral reticular nucleus, the interpeduncular nucleus, the raphe linearis, the paragigantocellularis, the inferior olive and ventral tegmental area. Overall, the neuropeptides most frequently present in the projection neurons were substance P, calcitonin gene-related peptide, galanin and cholecystokinin. Bombesin, neuropeptide Y, neurotensin and dynorphin were less common; and enkephalin was present in only a small percentage of projection neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Brainstem peptidergic neurons projecting to the medial and lateral thalamus and zona incerta in the rat. 768 Sep 39

The location of the cells giving rise to the tachykinergic innervation of the rat arcuate nucleus was studied by combining immunohistochemistry and retrograde axonal transport of a protein-gold complex (WGA-ApoHRP-gold). Small volumes (20 nl) of this marker were injected into the arcuate nucleus of the rat. Twenty-four to 30 h later, rats were injected with colchicine. After 24-h survival time, the paraformaldehyde-fixed brains were investigated for silver intensification of the gold particles and for tachykinin immunohistochemistry. Doubly immuno-silver-labeled cells were observed mainly in brainstem structures such as raphe nuclei, central gray pontine, and laterodorsal tegmental nucleus. Intranuclear and intrahypothalamic (ventromedial, dorsomedial, premamillary, and supramamillary) cell bodies were also doubly labeled, principally ipsilateral to the injection site. Minor afferent projections arise from the medial preoptic area. This anatomohistochemical study demonstrates that the arcuate nucleus receives intra- and extrahypothalamic tachykinergic inputs and shows that infundibular neurons undergo convergent tachykinergic influences.
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PMID:Tachykinergic afferents to the rat arcuate nucleus. A combined immunohistochemical and retrograde tracing study. 768

Neutral endopeptidase (E.C.3.4.24.11) was visualized at the ultrastructural level in the external zone of the rat median eminence by using 125I-labelled IgG of a monoclonal serum. A precise analysis of the localization of the immunolabelling, which appears in the form of individual stray silver grains, was undertaken. Among the 1,045 grains counted, 82% were localized over membrane appositions involving nerve endings only and nerve endings plus tanycytes. The difference between the real and a randomly generated population of grains was statistically significant. Our results provide morphological arguments in support of the view of a paracrine action of neuropeptides present in the median eminence especially enkephalins but possibly, substance P, angiotensin, cholecystokinin and neurotensin. These neuropeptides are known to be inactivated by neutral endopeptidase. The action of these peptides may be exerted on nerve endings (autocrine or paracrine) but an intervention on tanycytes cannot be excluded.
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PMID:Radioimmunocytochemical distribution of neutral endopeptidase (enkephalinase E.C.3.4.24.11) at the ultrastructural level in the rat median eminence. 768 59

Endopeptidase-24.11 is a widely distributed cell surface enzyme with a role in inactivating some neuropeptides and peptide hormones. In the central nervous system it has been implicated in the metabolism of enkephalins and tachykinins, neuropeptides which are expressed by neurons projecting to the substantia nigra. Two immunochemical methods have been used to reveal the ultrastructural localization of endopeptidase-24.11 and substance P in the substantia nigra of piglets. In the first approach, substance P was revealed by immunoperoxidase staining using the rat monoclonal antibody, NC1, and endopeptidase-24.11 by 1 nm colloidal gold using an affinity-purified rabbit polyclonal antibody, both being applied at the pre-embedding stage. NC1 was shown to be highly specific for substance P, with negligible cross-reactivity with neurokinins A and B. The specificity of the immunostaining was confirmed by processing all sections for both markers, even when only one primary antibody was applied. In the second approach, ultrathin cryosections were immunostained using gold particles of different diameters. In a survey of electron micrographs, 80% of the silver-enhanced gold particles were touching neuronal membranes, consistent with the known topology of endopeptidase-24.11. Endopeptidase-24.11 immunoreactivity was observed both on membranes of axons and on pre- and postsynaptic elements. Substance P immunoreactivity was seen within some boutons, apparently associated with vesicles, and in axons. In doubly stained sections, many examples of immunopositive gold-labelled boutons (i.e. endopeptidase-24.11-immunoreactive-positive) containing immunoperoxidase reaction product (i.e. substance P-immunoreactive-positive) were recorded. In ultrathin cryosections, substance P immunoreactivity was mainly observed in dense-core vesicles within boutons, some of which also showed membrane-associated gold particles marking endopeptidase-24.11 immunoreactivity. This is the first demonstration of endopeptidase-24.11 by immunogold at the electron microscopic level and the first demonstration of the ultrastructural co-localization of a membrane peptidase and its putative neuropeptide target. The results lend strong support to the view that endopeptidase-24.11 has a physiological role in the metabolism of substance P, but do not exclude a role in the inactivation of other neuropeptides.
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PMID:An immunoelectron microscopic study of pig substantia nigra shows co-localization of endopeptidase-24.11 with substance P. 768 69

Differential loss of neurons and terminals occurs in Huntington's disease. Neurons expressing preproenkephalin (PPE) appear to be more vulnerable than neurons expressing preprotachykinin and terminals in the lateral pallidum (containing enkephalin) are more affected than terminals in the medial pallidum (containing substance P). We used in situ hybridization histochemistry and emulsion autoradiography to quantify the number of PPE expressing neurons and the neuronal levels of PPE mRNA in striatum of individuals who died with Huntington's disease and normal controls. We found a grade-related decline in the number of PPE-labeled neurons per field in the striatum of individuals with Huntington's disease compared with controls. Three measures of the neuronal level of PPE mRNA, the mean number of silver grains per PPE neuron, the median number of grains per PPE neuron, and the percentage of PPE neurons with more than 30 grains, were all significantly reduced (41 to 80% of control) in Huntington's disease striatum. The magnitude of the reduction in levels of PPE mRNA per neuron was related to the grade of lesions. These data support the notion that decreased levels of PPE mRNA may account, in part, for the greater loss of enkephalin staining in lateral pallidal terminals compared with substance P staining in medial pallidal terminals. Decreased levels of PPE mRNA may result in clinical symptoms prior to the loss of neurons. The reduction in expression of PPE mRNA suggests that surviving striatal neurons may be affected by the expression of the Huntington's disease gene prior to their imminent cell death.
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PMID:Reduced expression of preproenkephalin in striatal neurons from Huntington's disease patients. 769 32


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