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)

Mystixins are synthetic peptides that inhibit plasma leakage after tissue injury. We sought to determine the mechanism of the antileakage effect of mystixins, with particular reference to the formation of endothelial gaps in postcapillary venules. Intravenous administration of mystixin-7, a prototype heptapeptide (p-anisoyl-Arg-Lys-Leu-Leu-D-Thi-Ile-D-Leu-NH2), decreased Evans blue leakage induced by substance P (5 microg/kg i.v.) with an ED50 (95% confidence limits) of 130 (76-211) microg/kg in trachea and 52 (27-100) microg/kg in skin of anesthetized F344 rats. Leakage was decreased without a reduction in the number or size of endothelial gaps, visualized by silver deposits after silver nitrate staining. The number of silver deposits per tracheal endothelial cell was 11.4 +/- 0.2 (mean +/- S.E.) after vehicle pretreatment vs. 13.0 +/- 0.8 after mystixin-7 pretreatment (100 microg/kg i.v.). Silver deposit diameter was unchanged at 1.4 +/- 0.1 micron. Mean arterial blood pressure dropped by a maximum of 38% from baseline for approximately 10 min after mystixin-7 (100 microg/kg i.v.), then recovered to a plateau at about 13% below baseline. The antileakage effect of mystixin-7 pretreatment in vivo was also demonstrated in aldehyde-fixed vessels perfused in situ with Evans blue at constant flow (skin, 79% reduction; trachea, 49% reduction), which suggests that mystixin can reduce leakage independent of its hypotensive effect. We conclude that the antileakage effect of mystixin does not depend on reducing the number or size of endothelial gaps, but instead could be caused by residual hypotension, which reduces the negative interstitial fluid pressure toward zero, or clogging of endothelial gaps.
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PMID:Anti-inflammatory mystixin peptides inhibit plasma leakage without blocking endothelial gap formation. 945 16

Neurogenic inflammation, in its original definition, the plasma leakage induced by stimulation of peripheral sensory nerves, occurs in the postcapillary venules of the skin and airways. Plasma leakage is accompanied by increased blood flow, which results from dilatation of arterioles. In skin, these phenomena are manifested as wheal and flare, respectively. Both phenomena are mediated by neuropeptides released from capsaicin-sensitive unmyelinated sensory nerve fibers. Substance P is the primary mediator responsible for plasma leakage, acting via tachykinin NK-1 receptors, whereas both calcitonin gene-related peptide and substance P induce vasodilatation. Sensory nerve transmitters also cause release of histamine from mast cells, which contributes substantially to plasma leakage in the skin, but less so in the airways. Substance P causes an increase in vascular permeability as a result of the focal, transient, and fully reversible formation of gaps, approximately 0.5 to 1.5 microns in diameter, located in the intercellular junctions of endothelial cells. The gaps can be visualized by silver nitrate staining of the endothelial cell borders, by lectin staining, or by scanning and transmission electron microscopy. Neurogenic inflammation can be inhibited by preventing the stimulation of sensory nerves, by presynaptic inhibition of neuropeptide release from sensory nerves, or by blocking neuropeptide receptors. The formation of endothelial gaps can also be inhibited by anti-inflammatory drugs that stabilize endothelial cells, such as beta-adrenergic agonists and steroids.
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PMID:Neurogenic inflammation in skin and airways. 948 20

The present study examined the effects of ageing on preprotachykinin-A (PPT-A) mRNA levels in discrete regions of the rat brain. Semiquantitative analysis of silver grains revealed a 16% statistically significant decrease in PPT-A mRNA in the shell of the nucleus accumbens (AcbSh), a 27.6% statistically significant lower level of PPT-A mRNA in the olfactory tubercle (Tu), a 19.2% and 31. 5% statistically significant decrease in PPT-A mRNA in the dorsal and ventral caudate-putamen (d-CPu) (v-CPu), respectively, a 30% statistically significant lower expression of PPT-A mRNA in the bed nucleus of the stria terminalis (BNST), a 33.7% statistically significant decrease in PPT-A mRNA in the habenula (Hb) and a 30% statistically significant decrease of PPT-A mRNA levels in the postero-dorsal part of the medial amygdala (MePD). No changes in PPT-A mRNA levels were found in the nucleus accumbens, core (AcbC), in the islands of Calleja (Icj), and in the medial preoptic area (mPOA). These results show that ageing of the central nervous system (CNS) is associated with widespread changes in tachykinin gene expression, suggesting that alteration in the tachykinergic system may have implications in the physio-pathology of the elderly.
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PMID:In situ hybridization analysis of preprotachykinin-A mRNA levels in young and old rats. 988 49

The distribution of substance P-, leucine-enkephalin-, tyrosine hydroxylase-, and serotonin-like immunoreactivities was studied in the forebrain of the silver lamprey and compared to other vertebrate groups. In silver lampreys, substance P and leucine-enkephalin provide a clear distinction between the pallium and subpallium as they do for gnathostomes. The pallium consists of three subdivisions which show striking similarities to the medial, dorsal and lateral pallia of gnathostomes. Boundaries of the preoptic area, the hypothalamus and posterior tubercle can be well defined by histochemical characteristics. These data refute the existence of a dorsal hypothalamic subdivision in silver lampreys and suggest rostral and caudal divisions of the hypothalamus.
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PMID:The chemoarchitecture of the forebrain of lampreys: evolutionary implications by comparisons with gnathostomes. 1034 42

A method for measuring endothelial damage caused by decompression was developed for vessels with a large radius. Segments of the pulmonary artery from pigs (8-12 wk old) were tested for endothelium damage using a system for recording changes in the tension in the vessel wall. Substance P (SP) was used as an endothelial-dependent dilation agonist. A significant decrease was found in the total response (Tmax) for SP as a result of endothelium damage, and the reduction in response was related to the number of bubbles. Furthermore, the sensitivity of the vessels to the agonist was significantly reduced after exposure to bubbles. Staining the endothelium with silver nitrate and light microscopy confirmed mechanical endothelium damage.
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PMID:Endothelial damage by bubbles in the pulmonary artery of the pig. 1035 78

Potent antinociception can be produced by electrical stimulation of spinally projecting noradrenergic neurons in the A7 catecholamine cell group and this effect is blocked by intrathecal injection of alpha2-adrenoceptor antagonists. Microinjection of substance P near A7 neurons also produces antinociception that is blocked by intrathecal injection of alpha2-adrenoceptor antagonists. These observations suggest that substance P produces antinociception by activating noradrenergic A7 neurons. However, it is not known whether this effect of substance P is produced by a direct or an indirect action on A7 neurons. Although light microscopic studies have demonstrated the existence of both substance P-containing axon terminals and neurokinin-1 receptors in the region of the A7 cell group, it is not known whether substance P terminals form synapses with noradrenergic A7 neurons. These experiments used double-labeling immunocytochemical methods and electron microscopic analysis to determine whether substance P-containing axons form synapses with noradrenergic neurons in the A7 cell group. Pre-embedding immunocytochemistry, combined with light and electron microscopic analysis, was used to provide ultrastructural evidence for synaptic connections between substance P-immunoreactive terminals labeled with immunoperoxidase and tyrosine hydroxylase-immunoreactive A7 neurons labeled with silver-enhanced immunogold. Tyrosine hydroxylase labeling was found in perikarya and dendrites in the A7 region, and substance P labeling was found in axons and synaptic terminals. Substance P-labeled terminals formed asymmetric synapses with tyrosine hydroxylase-labeled dendrites, but only a few of these were present on tyrosine hydroxylase-labeled somata. Substance P-labeled terminals also formed asymmetric synapses with unlabeled dendrites, and many unlabeled terminals formed both symmetric and asymmetric synapses with tyrosine hydroxylase-labeled dendrites. These results demonstrate that substance P neurons form a significant number of synapses with the dendrites of noradrenergic A7 neurons and support the conclusion that microinjection of substance P in the A7 cell group produces antinociception by direct activation of spinally projecting noradrenergic neurons.
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PMID:Ultrastructural evidence that substance P neurons form synapses with noradrenergic neurons in the A7 catecholamine cell group that modulate nociception. 1039 54

Silver nitrate stains the intercellular junctions of the endothelium and other cytoplasmic or membrane components. Two protocols are described for the silver staining of rat carotid endothelium that exclude the use of pressurized fixatives and simplify the technique previously described for rat aorta. The entire surface of the carotid endothelium was examined and several parameters (stigmata, granularity, clustering of anionic sites, transversal lines, weakening of silver lines and leukocyte adhesion) were evaluated. We studied the pattern of silver staining in two situations: (1) endothelial activation and (2) neurogenic inflammation. Endothelial activation was produced by the intravenous administration of a proinflammatory albumin or polyinosinic acid. Both products cause a marked increase in leukocyte adhesion concomitant with a decrease in argyrophilia and a weakness or loss of silver lines. Neurogenic inflammation, which is mediated by substances released from sensory nerves, was induced by the intravenous administration of substance P or capsaicin. Both stimuli produced an increase in argyrophilia and weakness or loss of silver lines. Substance P caused a clustering of anionic sites, whereas this phenomenon was more discrete with capsaicin. Nearly 80% of all examined rats (controls and inflammatory stimuli treated) showed endothelial membrane disruptions formed by clusters of cells often in the shape of streaks aligned with the long axis of the vessel. The detection of these discontinuities is important, as loss of endothelial integrity is central in the initiation of pathological events.
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PMID:Effect of inflammatory stimuli on the silver staining pattern of the rat carotid endothelium. 1042 14

Silver staining and high-resolution electrophoretic methods have been used to compare the protein composition of rat parotid saliva evoked in response to (i) parasympathetic stimulation (including the nonadrenergic, noncholinergic, atropine-associated secretion), (ii) sympathetic stimulation, or (iii) the infusion of neuropeptides with secretagogue activity (substance P, calcitonin gene-related peptide, neuropeptide Y, or vasoactive intestinal peptide). The different stimuli influenced the protein concentration and flow rate of the evoked secretion but had little effect upon the protein composition of the saliva. In contrast to earlier studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Coomassie blue staining, the combination of silver staining and two-dimensional electrophoresis (2-DE) revealed many newly detected proteins. The results indicate that the protein composition of rat parotid saliva is more complex than previously reported but is unaffected by the mode of stimulation.
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PMID:High-resolution electrophoretic analysis of rat parotid salivary proteins. 1042 58

Peptidergic innervation of the human cerebral vasculature has not yet been described in detail and its role in the maintenance of cerebral autoregulation still needs to be established. Similarly, few data exist on the innervation of vascular malformations. The aim of this study was to clarify the peptidergic innervation patterns of human cerebral arteries of various sizes, and, for the first time, that of saccular aneurysms. Light microscopic study of whole-mount preparations of human cerebral arteries and aneurysm sacs resected either during tumor removal or after neck-clipping were carried out by means of silver-intensified light microscopic immunocytochemistry visualizing neuropeptide-Y, calcitonin gene-related peptide and substance P immunoreactivity. Systematic morphological investigations confirmed the presence of longitudinal fiber bundles on the adventitia and a network-like deeper peptidergic system at the adventitia-media border, while in smaller pial and intraparenchymal vessels, only sparse longitudinal immunopositive axons could be detected. The innervation pattern was totally absent in the wall of saccular aneurysms with the complete disappearance of peptidergic nerve fibers in some areas. To the best of our knowledge neither the disappearance of this network on small pial and intraparenchymal vessels, nor the absence of an innervation pattern in saccular aneurysms have been described before. Nonhomogeneous peptidergic innervation of the human cerebral vascular tree might be one of the factors responsible for the distinct autoregulatory properties of the capacitance and resistance vessels. Malfunction of this vasoregulatory system might lead to the impairment of autoregulation during pathological conditions such as subarachnoid hemorrhage.
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PMID:Peptidergic innervation of human cerebral blood vessels and saccular aneurysms. 1050 44

Altered thyroid statuses are associated with autonomic disorders. Medullary thyrotropin-releasing hormone (TRH) and substance P (SP) regulate autonomic nervous activity. The influences of thyroid statuses on TRH and SP gene expressions in the caudal raphe nuclei and the parapyramidal regions were studied using quantitative in situ hybridization histochemistry. In male rats thyroidectomized (Tx) for 30 days, the serum T4 levels decreased by 64% and the medullary pro-TRH mRNA signals (silver grains per neuron) significantly increased by 32-45%. These changes were prevented by daily i.p. T4 (2 microg/100 g) injection in Tx rats. In sham operated/T4 (20 microg/100 g, daily) injected rats, T4 levels significantly increased by 88% and the silver grains decreased by 38-40%. Medullary SP mRNA signals were not significantly changed by altering thyroid status. These results support the concept that thyroid hormone regulates medullary TRH gene expression by negative feedback.
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PMID:Hyperthyroidism decreases thyrotropin-releasing hormone gene expression in the caudal raphe nuclei and the parapyramidal regions in rats. 1061 37


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