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 medium formulation and robust process modeling for anti-HIV peptide (T-20) production by recombinant Escherichia coli overexpression were studied by employing a crossed experimental design. The crossed design, a mixture design combined with process factor (induction duration), was used to find the optimal medium formulation and process time. The optimal settings for three major components (7.75 mL of NPK sources, 5.5 mL of glucose, and 11.75 mL of MgSO4) characterized by %T-20 (14.45%), the proportion of peptide to the total protein, were observed in a total of 100 mL of medium inducted at an optical density of 0.67 with 0.7 mM isopropyl-beta-D-thiogalactopyranoside) for a 3-h induction duration at shake-flask scale. These conditions were further investigated to find robust process conditions (8.2 mL of NPK sources, 5.6 mL of glucose, and 11.3 mL of MgSO4, and a 3.5-h induction duration time) for T-20 production (13.9%) by applying propagation of error.
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PMID:Statistical medium formulation and process modeling by mixture design of experiment for peptide overexpression in recombinant Escherichia coli. 1705 57

Cryptosporidiosis, caused by the protozoan parasite Cryptosporidium, causes self-limited diarrhea in immunocompetent hosts and severe life-threatening diarrhea in AIDS patients. Highly active antiretroviral therapy has been used to effectively treat cryptosporiosis in some but not all AIDS patients. Therefore, there is an urgent need for innovative drugs to treat this disease. Cryptosporidium infection results in intestinal pathophysiological changes such as glucose malabsorption, increased chloride ion (Cl(-)) secretion, and epithelial barrier disruption, leading to disease pathogenesis. In order to develop tools to combat this opportunistic pathogen, it is vital to understand mediators involved in disease pathogenesis. Substance P (SP), a neuropeptide and pain transmitter, is located in the gastrointestinal tract. SP can cause Cl(-) secretion in human gastrointestinal explants. However, its role in cryptosporidiosis has not been fully studied. Jejunal samples from macaques before and after Cryptosporidium parvum infection were assayed for SP and SP receptor mRNA and protein levels by reverse transcription-PCR and by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The role of SP in pathophysiological alterations, such as Cl(-) secretion and glucose malabsorption, was studied using tissues derived from macaques infected with C. parvum by the Ussing chamber technique. SP and SP receptor mRNA and protein expression levels were increased in jejunal samples following C. parvum infection and were accompanied by increased basal ion secretion and glucose malabsorption. In vitro treatment of samples obtained from infected macaques with the SP receptor antagonist aprepitant (Emend; Merck, Whitehouse Station, NJ) completely reversed the increase in basal ion secretion and corrected the glucose malabsorption. Our findings raise the possibility of using SP receptor antagonists for the treatment of symptoms associated with cryptosporidiosis.
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PMID:Substance P is responsible for physiological alterations such as increased chloride ion secretion and glucose malabsorption in cryptosporidiosis. 1715 91

Substance P (SP) is involved in the pathophysiology of several psychiatric disorders and is considered a central stress neurotransmitter. Endogenous SP does not inhibit the initial extent of the HPA axis response to restraint stress, but reduces the duration of the stress suggesting that SP plays an important role in the transition between acute and chronic stress. Stress hormones can alter metabolic functions in white adipose tissue and liver. The HPA axis is the endocrine pathway that promotes lipolysis elevating free fatty acid levels (FFA) in blood, besides indirectly causing hyperglycemia. In the present study, changes in the blood levels of stress markers in the anxiogenic-like effects of SP, as evaluated on the elevated plus-maze (EPM), were studied in adult male rats. Serum corticosterone was used as the traditional stress marker, while the plasma FFA and glucose were used as alternative anxiety/stress markers. Our findings show: (a) elevated corticosterone levels, confirming the aversive situation induced by SP (behaviorally assessed in the EPM) and indicating SP as a "chemical" stressor; (b) elevated levels of FFA and glucose, indicators of stress-induced mobilization of energy substrates, confirming the stressor effect of SP; (c) FFA levels can be used as an accurate, sensitive and reliable index of acute stress situations, including in the anxiogenic-like effect of SP, with the FFA response being as good as corticosterone as a stress marker in this case; (d) NK1 receptors involvement in the underlying mechanisms of the behavioral and metabolic effects of SP. Finally, our study indicates that some of these physiological variables are positively related to the stressor intensity.
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PMID:Involvement of NK1 receptors in metabolic stress markers after the central administration of substance P. 1754 Apr 63

Ghrelin is produced by A-like cells (ghrelin cells) in the mucosa of the acid-producing part of the stomach. The mobilization of ghrelin is stimulated by nutritional deficiency and suppressed by nutritional abundance. In an attempt to identify neurotransmitters and regulatory peptides that may contribute to the physiological, nutrient-related regulation of ghrelin secretion, we challenged the ghrelin cells in situ with a wide variety of candidate messengers, including known neurotransmitters (e.g. acetylcholine, catecholamines), candidate neurotransmitters (e.g. neuropeptides), local tissue hormones (e.g. serotonin, histamine, bradykinin, endothelin), circulating gut hormones (e.g. gastrin, CCK, GIP, neurotensin, PYY, secretin) and other circulating hormones/regulatory peptides (e.g. calcitonin, glucagon, insulin, PTH). Microdialysis probes were placed in the submucosa of the acid-producing part of the rat stomach. Three days later, the putative messenger compounds were administered via the microdialysis probe (reverse microdialysis) at a screening dose of 0.1 mmol l(-1) for regulatory peptides and 0.1 and 1 mmol l(-1) for amines and amino acids. The rats were awake during the experiments. The resulting microdialysate ghrelin concentration was monitored continuously for 3 h (radioimmunoassay), thereby revealing stimulators or inhibitors of ghrelin secretion. Dose-response curves were constructed for each candidate messenger that significantly (p<0.05) affected ghrelin mobilization at the screening dose. Peptides that showed a (non-significant) tendency to affect ghrelin release at the screening dose were also given at a dose of 0.3 or 1 mmol l(-1). Adrenaline, noradrenaline, endothelin and secretin stimulated ghrelin release, while somatostatin and GRP inhibited. Whether these agents act directly or indirectly on the ghrelin cells remains to be investigated. All other candidate messengers were without measurable effects, including acetylcholine, serotonin, histamine, GABA, aspartic acid, glutamic acid, glycine, VIP, PACAP, CGRP, substance P, NPY, PYY, PP, gastrin, CCK, GIP, insulin, glucagon, GLP and glucose.
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PMID:Secretion of ghrelin from rat stomach ghrelin cells in response to local microinfusion of candidate messenger compounds: a microdialysis study. 1757 35

Rats that had been injected with monosodium glutamate (MSG) neonatally were studied for up to 70 weeks and compared with age-matched control rats to study changes in glucose tolerance and in sympathetic and sensory nerves. At 61 and 65 weeks of age, there were significant differences in glucose tolerance between the MSG and control groups, and the MSG group had raised fasting blood glucose. These changes were not associated with changes in the number of beta-cells in the islets of Langerhans. In addition, the diabetic MSG-treated rats had central obesity and cataracts. Hypoalgesia to thermal stimuli was present in MSG-treated rats as early as 6 weeks and persisted at 70 weeks. However, no differences were observed in the distribution of substance P, the neurokinin-1 receptor or calcitonin gene-related peptide in the dorsal horn of L3-L5 at this age (70 weeks). Diabetic MSG-treated animals at 65 and 70 weeks of age had significantly reduced noradrenaline concentrations in the heart, tail artery and ileum, while concentrations in the adrenal gland and corpus cavernosum were significantly increased. There was also a significant increase in adrenal adrenaline, dopamine and serotonin, largely attributable to changes in weight of the adrenal gland in the MSG-treated animals. The results indicate that MSG-treated animals develop a form of type II diabetes by about 60 weeks of age, and that there are significant changes in amine levels in various tissues associated with these developments.
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PMID:Sensory and autonomic nerve changes in the monosodium glutamate-treated rat: a model of type II diabetes. 1791 58

The vagal nerve conveys primary afferent information from the intestinal mucosa to the brain stem. Activation of vagal afferent fibers results in inhibition of food intake, gastric emptying, and stimulation of pancreatic secretion. Afferents nerves terminating near to the mucosa are in a position to monitor the composition of the luminal contents. As afferents do not project directly into the lumen, their activation depends on an intermediary step, i.e. neuronal activation by a secondary substance released from within the mucosal epithelium. This review addresses the role for both cholecytokinin (CCK) and serotonin (5-HT) released from enteroendocrine cells and acting as paracrine agents on the terminals of vagal afferents in responses to a number of luminal signals. CCK acted on both high- and low-affinity CCK-A receptors present on distinct vagal primary afferent neurons. Neurons of the nodose ganglia respond to intraduodenal perfusions of maltose, glucose, and hypertonic saline. These neurons were also sensitive to exogenous luminally applied 5-HT at concentrations that mimic physiologic levels. Intravenous administration of a 5-HT3 antagonist blocked these responses suggesting that nodose neuronal responses to luminal osmolarity and to the digestion products of carbohydrates are dependent on the release of endogenous 5-HT from the mucosal enterochromaffin (EC) cells, which acts on the 5-HT3 receptors on vagal afferent fibers to stimulate vagal afferent neurons. Double-labeling studies revealed that nodose neurons responded to 5-HT-dependent luminal stimuli contain mainly glutamate and substance P. Over the past year or so it has become clear that there are multiple possible excitatory inputs to a common vagal afferent route with synergistic interactions being common. The nodose ganglion contains neurons that may possess only high- or low-affinity CCK-A receptors or 5-HT3 receptors. Some neurons that express high-affinity CCK-A receptors also express 5-HT3 receptors and (or) secretin receptors. Pre-exposure to luminal 5-HT may augment the subsequent response to a subthreshold dose of CCK. Synergistic interaction between CCK and secretin also occurs at the nodose ganglia; this is mediated by high affinity CCK-A receptor. This may explain the robust postprandial secretion of enzyme, bicarbonate, and fluid despite the modest increase in CCK after a meal. Some neurons that possess low-affinity CCK-A receptor colocalize with leptin receptors (OB-Rs). These neurons also respond to mechanical distention. Interaction between CCK-A receptor and OB-Rs in these neurons likely facilitates leptin mediation of short-term satiety.
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PMID:Sensory signal transduction in the vagal primary afferent neurons. 1797 8

Little is known about the effect of diabetes mellitus (DM) on transient receptor potential vanilloid 1 (TRPV1) located in cardiac sensory nerves. This study was performed to test the changes of TRPV1 and its main neuropeptides in diabetic hearts. DM was induced by intraperitoneal injection of streptozotocin (STZ) in C57BL/6J mice. The protein and mRNA expression of TRPV1, calcitonin gene-related peptide (CGRP) and substance P (SP) levels in hearts were measured, respectively. Compared with control mice, blood glucose was significantly increased in diabetic mice (P<0.05), while the protein and mRNA expression of TRPV1, CGRP and SP levels in hearts were essentially reduced in diabetic mice (P<0.05). TRPV1 and its main neuropeptides, CGRP and SP, in hearts were impaired during DM.
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PMID:Impaired transient receptor potential vanilloid 1 in streptozotocin-induced diabetic hearts. 1837 39

Exosomes are small membrane vesicles (30-100 nm) with an endosome-derived limiting membrane that are secreted by a diverse range of cell types. We provide here the first evidence for the presence of exosome-like vesicles in snake venom. We isolated vesicles from fresh venom from Gloydius blomhoffii blomhoffii by gel-filtration. We found that the vesicles showed a typical exosome-like size and morphology as analyzed by electron microscopy. We observed that the vesicles contained dipeptidyl peptidase IV, aminopeptidase A, ecto-5'-nucleotidase and actin. Vesicle preparations truncated bioactive peptides such as angiotensin II, substance P, cholecystokinin-octapeptide, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. The role of these vesicles is still unknown, but they may affect blood pressure and glucose homeostasis following envenomation.
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PMID:Exosome-like vesicles in Gloydius blomhoffii blomhoffii venom. 1838 31

Cryptosporidiosis, caused by the protozoan parasite Cryptosporidium parvum, causes self-limited diarrhea in normal hosts but can cause life-threatening diarrhea for immunosuppressed patients. There is an urgent need for new drugs to treat this chronic disease. Cryptosporidium parvum infection is associated with intestinal structural and pathophysiologic changes, including villi blunting and glucose malabsorption. Substance P (SP), a neuropeptide and pain transmitter, is associated with the gastrointestinal tract and is elevated in humans and macaques after experimental C. parvum challenge. To examine the relevance of SP in the pathogenesis of cryptosporidiosis, and to determine if SP receptor antagonism can be employed for treatment of cryptosporidiosis in immunosuppressed hosts, we used an immunosuppressed murine model (dexamethasone-immunosuppressed mice) that is frequently utilized for examining chemotherapeutic potential of drugs. Quantitative ELISA was used to measure intestinal SP levels in immunosuppressed mice with, and without, C. parvum infection. Intestinal physiological alterations, as studied by the Ussing chamber technique, plus weight change, fecal oocyst shedding, and villi measurements, were compared in infected mice with, and without, SP receptor antagonist (aprepitant) treatment. Immunosuppressed mice infected with C. parvum demonstrated increased SP levels as well as physiological alterations (glucose malabsorption), weight loss, fecal oocyst shedding, and structural alterations (increased intestinal villi blunting) compared to uninfected mice. Each of these defects was significantly inhibited by aprepitant treatment. These studies demonstrate the potential of SP receptor antagonism for treatment of pathogenesis of cryptosporidiosis in immunosuppressed hosts.
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PMID:Substance P receptor antagonism for treatment of cryptosporidiosis in immunosuppressed mice. 1857 2

Ochrobactrum anthropi strain AD2 was isolated from the waste water treatment plant of an oil refinery and was identified by analysis of the sequence of the gene encoding 16S rDNA. This bacterium produced exopolysaccharides in glucose nutrient broth media supplemented with various hydrocarbons (n-octane, mineral light and heavy oils and crude oils). The exopolysaccharide AD2 (EPS emulsifier) synthesized showed a wide range of emulsifying activity but none of them had surfactant activity. Yield production varied from 0.47 to 0.94 g of EPS l(-1) depending on the hydrocarbon added. In the same way, chemical composition and emulsification activity of EPS emulsifier varied with the culture conditions. Efficiency of the EPS emulsifier as biostimulating agent was assayed in soil microcosms and experimental biopiles. The AD2 biopolymer was added alone or combined with commercial products frequently used in oil bioremediation such as inorganic NPK fertilizer and oleophilic fertilizer (S200 C). Also, its efficiency was tested in mixture with activated sludge from an oil refinery. In soil microcosms supplemented with S200 C+EPS emulsifier as combined treatment, indigenous microbial populations as well as hydrocarbon degradation was enhanced when compared with microcosms treated with NPK fertilizer or EPS emulsifier alone. In the same way EPS emulsifier stimulated the bioremediation effect of S200 C product, increasing the number of bacteria and decreasing the amount of hydrocarbon remained. Finally, similar effects were obtained in biopile assays amended with EPS emulsifier plus activated sludge. Our results suggest that the bioemulsifier EPS emulsifier has interesting properties for its application in environment polluted with oil hydrocarbon compounds and may be useful for bioremediation purposes.
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PMID:Efficiency of the EPS emulsifier produced by Ochrobactrum anthropi in different hydrocarbon bioremediation assays. 1878 47


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