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: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of sepsis on plasma levels of various gut peptides was studied in rats. Sepsis was induced by cecal ligation and puncture (CLP); control animals underwent sham operation. Sixteen hours after CLP or sham operation, portal and systemic blood was drawn, and plasma levels of gastrin, vasoactive intestinal peptide (VIP), secretin, peptide YY (PYY), gastrin-releasing peptide (GRP), and substance P were determined by radioimmunoassay. Plasma levels of gastrin, VIP, PYY, and secretin were elevated in septic rats compared with nonseptic animals, with the highest levels noted in portal blood. There was no effect of sepsis on GRP or substance P levels. In other experiments, human recombinant interleukin 1 alpha (IL-1 alpha) or recombinant tumor necrosis factor alpha (TNF alpha) was injected intraperitoneally (300 micrograms/kg body weight in 3 divided doses over 16 hours). There was no change in plasma levels of gut peptides after IL-1 alpha injection. TNF alpha induced elevation of PYY levels in portal plasma with no change in other gut peptide levels. The results suggest that sepsis stimulates release of certain gut peptides and that TNF, but not IL-1, may be partly responsible for this response. The mechanism of the release of gut peptides and its significance in the pathophysiologic changes induced by sepsis remain to be determined.
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PMID:Effect of sepsis or cytokine administration on release of gut peptides. 173 67

The aim of this work was to study the hypothesis that the release of vasoactive neuropeptides may be related to the hemodynamic changes and severity of disease in human sepsis and septic shock. Twenty-two patients diagnosed with sepsis and treated in medical wards with standard supportive therapy and twenty patients admitted to a medical intensive care unit because of septic shock were studied Twenty healthy volunteers in a similar age range were enrolled as control group. Blood samples were taken at onset and every 12 hours on the following day after hospital admission to measure plasma concentrations of calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and substance P (SP). Clinical and biochemical variables were measured simultaneously. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was calculated on admission. From the day of admission, septic shock patients had significantly higher plasma CGRP-like immunoreactivity levels than patients with sepsis, as well as both groups of patients compared to control subjects. Plasma NPY-like immunoreactivity levels in patients with either sepsis or septic shock was significantly increased, and plasma SP-like immunoreactivity levels significantly reduced compared to those in controls. Plasma CGRP levels at study entry correlated with the APACHE II score (r = 0.71, p < 0.01), as well as with the cardiac index (r = 0.61, p < 0.05) and systemic vascular resistance index (r = -0.62, p < 0.05). Our data suggest that both CGRP and NPY, but not SP, are increasedly released into the circulation during the development of human sepsis and septic shock. In patients with sepsis the vasoconstriction mediated by the release of NPY appears to counterbalance the vasodilatory effect of CGRP. In septic shock patients, however, the release of NPY might be inadequately low to overcome the widespread CGRP-induced vasodilation.
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PMID:Changes in plasma concentrations of vasoactive neuropeptides in patients with sepsis and septic shock. 752 63

Increased release of endothelium-derived relaxing factor/nitric oxide has been proposed as the final common pathway for vasodilator responses to gram-negative lipopolysaccharide (endotoxin). To test this hypothesis, we examined endothelium-dependent and endothelium-independent vasodilator agents in vascular smooth muscle isolated from guinea pigs 16 hours after injection of saline (control group) or induction of Escherichia coli endotoxemia; aortic rings (approximately 1 mm in diameter) were studied with standard isometric tension techniques. Endotoxemia resulted in a significant loss of vasodilator responses to the endothelium-dependent receptor agonists acetylcholine (10(-10)-10(-5) M) and ADP (10(-8)-10(-5) M). In contrast, endotoxemia did not affect vasodilator responses to either the endothelium-dependent receptor agonist substance P (10(-11)-10(-7) M), the endothelium-dependent and receptor-independent agonist A23187 (10(-9)-10(-6) M), or the endothelium-independent agonist nitroprusside (10(-10)-10(-4) M). The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) inhibited the vasodilator response to acetylcholine more in vessels from lipopolysaccharide-injected than control guinea pigs. Unexpectedly, L-NAME converted the endothelium-dependent vasodilator action of ADP to an endothelium-dependent vasoconstrictor response that was blocked individually by the cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor dazoxiben, and the thromboxane A2 receptor antagonist SQ29548. We conclude that in vivo endotoxemia inhibits the constitutive isoform of nitric oxide synthase in endothelial cells by selectively disrupting receptor-coupled activation mechanisms shared by acetylcholine and ADP. Furthermore, since L-NAME unmasks a thromboxane A2-mediated vasoconstrictor action of the endogenous purinoceptor agonist ADP, drugs that inhibit nitric oxide synthase could exacerbate sepsis-induced vasoconstriction and ischemia by synergizing with lipopolysaccharide-induced inhibition of endothelial nitric oxide synthase.
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PMID:Selective inhibition of endothelium-dependent vasodilator capacity by Escherichia coli endotoxemia. 767 34

This study is aimed to investigate the relationship between plasma concentrations of nitrite and nitrate as a measure of ongoing nitric oxide (NO) production, the vasodilatory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP), endotoxemia and hemodynamic changes in human septic shock. Thirteen patients with septic shock were studied within 6 h after the development of hypotension. Hemodynamic measurements and blood samples were recorded simultaneously at 2-h intervals from study admission. Eighteen normotensive patients with sepsis were included as control group of patients. On study entry, circulating levels of endotoxin did not relate to either CGRP or nitrite and nitrate plasma values. Septic shock patients had significantly higher plasma CGRP, and nitrite and nitrate concentrations, at each of the four time points, than patients with sepsis, as well as both groups of patients compared to normal subjects. No differences were found in plasma SP levels between the two groups of patients. For pooled data from all septic shock patients and measurements (n = 52), both plasma concentrations of CGRP and nitrite and nitrate were inversely correlated, independently from each other, to systemic vascular resistance. On study admission and at 2-h intervals, plasma CGRP concentrations correlated directly with nitrite and nitrate values. Our observations, thus, point to CGRP acting in concert with NO as important mediators responsible for hypotension in human septic shock.
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PMID:Relationship between circulating levels of calcitonin gene-related peptide, nitric oxide metabolites and hemodynamic changes in human septic shock. 888 78

Calcitonin gene-related peptide [CGRP]--a powerful vasodilator, is a 37 amino acid peptide that is find primarily in the central and peripheral nervous system. It affects the regulation of local blood flow, smooth muscle tone and glandular secretion. It is an endocrine regulator and in the lungs it also exerts a bronchoconstricting effect. CGRP has a proliferative effect on human endothelial cells. Therefore, it is important for the formation of new vessels, example, in ischemia, inflammations, and in the healing of wounds. Plasma levels of CGRP are increase in patients with chronic cardiac failure and sepsis, indicating that CGRP may be another important peptide in chronic illness. We have therefore measured the release of this peptide and another sensory peptide [Substance P (SP)]; a vasoconstrictor peptide [Endothelin (ET)]; and a perivascular peptide [Neuropeptide Y (NPY)], within 24 hours of injury, in the plasma of patients with soft tissue injury. Neuropeptides were measure by enzyme immunoassay technique. Median: (lower quartile-upper quartile) in pmol/L CGRP level was elevated in patients [50.37: (12.4-110.9)] compared to controls [13.9: (10.9-36.96)] p<0.05; Endothelin and NPY did not vary much between groups p=NS; ET: patients [8.7: (1.7-87.1), controls 8.8: (1.7-32.9)]; NPY: Patients [11.7: (10.5-14.99), controls 11: (10.3-12.8)]. SP was increase in patients [302.3: (79.9-707.3)], than controls [5.6: (3.2-36.6)] p<0.05. Furthermore, Elastase (a decisive marker for inflammation and infectious complications), was measure (ng/L), and found to be slightly higher in patients (102: 25.5-223), than controls (91.8: 45.9-127). In summary, plasma levels of sensory peptides increased significantly, in patients with soft tissue injury, in contrast to vasocostrictor peptides that remained unchanged. These sensory peptides may yet be another group of neuromodulators playing a significant role in immune, pain, inflammatory and wound healing in soft tissue injury patients.
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PMID:Calcitonin gene-related peptide and other neuropeptides in the plasma of patients with soft tissue injury. 1050 54

Calcitonin gene-related peptides (CGRP) is a 37 amino acids peptide that has a proliferative effect on human endothelial cells, and is therefore important for the formation of new vessels and wound healing. As indicated by in vitro and animal studies, CGRP is also a potent vasodilator for cutaneous, cerebral, coronary vessels, a bronchoconstrictor and endocrine regulator. Systemic CGRP increase in patients with soft tissue injuries, chronic illness and sepsis, indicates that CGRP may yet be an important peptides in chronic illness. Although CGRP is a potent vasodilator, systemic vascular resistance does not increase in some patients with high CGRP levels. We questioned whether any changes occur in systemic CGRP levels in patients with one of the most common types of bone fractures especially in the elderly. In order to evaluate further the role of this peptide in these patients, a vasoconstictor (Endothelin-1 [ET]) and another sensory neuropeptide (Substance P [SP]) were measured within 24 h of injury. A sample was obtained on admission (day 1) and within 24 h post admission (day 2) in patients with fracture neck of femur (mean age 77.6, +/- 10 years, n = 20) and compared with healthy controls (51, +/- 26.8 years, n = 20). Peptides and hormones were measured by ELISA techniques. Mean (ng/l) CGRP was elevated in patients (day 1 [314 +/- 195] and day2 [209.2 +/- 150]); compared to controls (68.2 +/-31) P<0.005. Endothelin was non-significantly higher in day-2 (day 1 [28.5 +/-31], day2 [37.4 +/-38], controls [24.2 +/-21]) P = NS. SP maintained higher levels within 24 h after injury (day 1 [85.7 +/- 94], and day2 [80.9 +/- 91.8]) compared to controls, P< 0.05. Furthermore, Elastase (a decisive marker for inflammation and infectious complications) was found to be higher in patients being pronounced in day 2 than in day 1 (day 1 [200 +/-136], day2 [139 +/-118]). Creatine kinase and myoglobin were measured and found to be notably higher in patients. These peptides may be yet another group of cytokines playing significant role in immunologic, inflammatory complications or wound healing in this group of patients.
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PMID:Elevation of plasma CGRP and SP levels in orthopedic patients with fracture neck of femur. 1098 28

Acute pancreatitis is a common clinical condition. The exact mechanisms by which diverse etiological factors induce an attack are unclear but once the disease process is initiated, common inflammatory and repair pathways are invoked. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction; if marked, this leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicemia, severe burns and trauma. Potentially, there is a therapeutic window between symptom onset and the development of distant organ damage in acute pancreatitis, when anti-inflammatory therapy may be of use. Recent studies conducted by us and other investigators have established the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, CINC/GRO-alpha, MCP-1, PAF, IL-10, CD40L, C5a, ICAM-1, and Substance P in acute pancreatitis and the resultant MODS. It is reasonable to speculate that elucidation of the key mediators in acute pancreatitis coupled with the discovery of specific inhibitors will make it possible to develop a clinically effective anti-inflammatory therapy.
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PMID:Novel therapeutic targets for acute pancreatitis and associated multiple organ dysfunction syndrome. 1456 Nov 81

Inflammatory response leading to organ dysfunction and failure continues to be the major problem after injury in many clinical conditions such as sepsis, severe burns, acute pancreatitis, haemorrhagic shock, and trauma. In general terms, systemic inflammatory response syndrome (SIRS) is an entirely normal response to injury. Systemic leukocyte activation, however, is a direct consequence of a SIRS and if excessive, can lead to distant organ damage and multiple organ dysfunction syndrome (MODS). When SIRS leads to MODS and organ failure, the mortality becomes high and can be more than 50%. Acute lung injury that clinically manifests as acute respiratory distress syndrome (ARDS) is a major component of MODS of various aetiologies. Inflammatory mediators play a key role in the pathogenesis of ARDS, which is the primary cause of death in these conditions. This review summarizes recent studies that demonstrate the critical role played by inflammatory mediators such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, platelet activating factor (PAF), IL-10, granulocyte macrophage-colony stimulating factor (GM-CSF), C5a, intercellular adhesion molecule (ICAM)-1, substance P, chemokines, VEGF, IGF-I, KGF, reactive oxygen species (ROS), and reactive nitrogen species (RNS) in the pathogenesis of ARDS. It is reasonable to speculate that elucidation of the key mediators in ARDS coupled with the discovery of specific inhibitors would make it possible to develop clinically effective anti-inflammatory therapy.
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PMID:Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. 1474 96

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1 versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic 'overshooting' with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.
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PMID:Cytokine dysregulation, inflammation and well-being. 1616 5

Preprotachykinin-A (PPT-A) gene products substance P and neurokinin-A have been shown to play an important role in neurogenic inflammation. To investigate the role of PPT-A gene products in lung injury in sepsis, polymicrobial sepsis was induced by cecal ligation and puncture in PPT-A gene-deficient mice (PPT-A(-/-)) and the wild-type control mice (PPT-A(+/+)). PPT-A gene deletion significantly protected against mortality, delayed the onset of lethality, and improved the long-term survival following cecal ligation and puncture-induced sepsis. PPT-A(-/-) mice also had significantly attenuated inflammation and damage in the lungs. The data suggest that deletion of the PPT-A gene may have contributed to the disruption in recruitment of inflammatory cells resulting in protection against tissue damage, as in these mice the sepsis-associated increase in chemokine levels is significantly attenuated.
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PMID:Preprotachykinin-A gene products are key mediators of lung injury in polymicrobial sepsis. 1651 52


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