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)

Recent evidence indicates that soybean, which is widely used in animal nutrition, could directly alter intestinal ion and nutrient transport. However, the mechanisms involved are still unknown. The aim of the study was to investigate the effect of three differently treated soybean products on the glucose and Cl- transport capacity in porcine small intestine by the Ussing chamber technique. Jejunal and ileal piglet epithelial tissues were pre-incubated with extracts of raw soybean flour (RSF), heated soybean flour (HSF), or ethanol heat-treated soybean protein concentrate (SPC). The Na(+)-dependent glucose co-absorption capacity was then measured as an increase in the short-circuit current (ISC) after luminal addition of D-glucose. The effect of the soybean products on cAMP-dependent Cl- secretion was measured as the increase in ISC after the addition of the phosphodiesterase inhibitor, theophylline, while nervous regulation of Cl- secretion was investigated by the addition of the enteric neurotransmitters; 5-hydroxytryptamine (5-HT), substance P and vasoactive intestinal polypeptide (VIP). Incubation with RSF and HSF induced a 30% decrease of the Na(+)-dependent glucose absorption capacity in the jejunum. The effect was similar for RSF in the ileum. Theophylline-induced secretion was decreased by 30% after incubation with RSF, HSF and SPC but only in the jejunum. 5-HT-, substance P- and VIP-induced secretion were not altered by incubation with soybean extracts except in the HSF-incubated where the substance P-induced secretion was significantly reduced. In conclusion, soybean contains ethanol-sensitive heat-insensitive compounds impairing Na(+)-dependent glucose absorption in the jejunum and ileum, and ethanol- and heat-insensitive compounds causing an acute impairment of cAMP-dependent jejunal secretion.
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PMID:Soybean impairs Na(+)-dependent glucose absorption and Cl- secretion in porcine small intestine. 1500 70

Excitation of primary afferent neurons stimulates the expression of cytokines and nerve growth factor (NGF) in innervated tissues. Since NGF is a neurotrophic and immunomodulatory factor contributing to inflammatory hyperalgesia and tissue response to injury, this study was conducted in order to investigate the mechanisms by which afferent neuron stimulation by topical application of capsaicin increases NGF in the rat skin. Thereby it was sought to identify possible targets for pharmacological modulation of NGF biosynthesis. Topical capsaicin (>1 mg/ml ethanol) caused a concentration- and time-dependent increase in the concentration of NGF in rat skin. The capsaicin-induced increase of NGF was not significantly affected by indomethacin administered at a dose (2 mg/kg) that abolishes prostaglandin E2 biosynthesis. The NGF increase was suppressed by treatment of rats with the selective tachykinin NK1 receptor antagonist SR140333 (0.1 mg/kg), and by the beta adrenergic agonist terbutaline (0.3 mg/kg). The effect of terbutaline was reversed by the beta adrenergic antagonist propranolol (1 mg/kg). Terbutaline also inhibited the increase in NGF caused by intraplantar injection of the NK1 receptor agonist substance P (SP), but did not significantly affect that caused by carrageenan. The results show that topical administration of capsaicin causes a primarily NK1 receptor-dependent increase in the NGF content of rat skin, which is susceptible to inhibition by beta adrenergic agonists. These observations not only suggest regulation of skin NGF biosynthesis by afferent neuronal and adrenergic mechanisms, but also indicate possible targets for pharmacological modulation of skin NGF biosynthesis.
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PMID:Beta adrenergic inhibition of capsaicin-induced, NK1 receptor-mediated nerve growth factor biosynthesis in rat skin. 1549 87

We performed experiments in spinal cords isolated from neonatal rats to probe the mechanisms responsible for hyperresponsiveness of the population excitatory evoked potential (pEPSP) observed on washout of the volatile anesthetics halothane and isoflurane (1 minimal alveolar anesthetic concentration equivalent, MAC) compared with that observed after an anesthetic concentration of ethanol. After 30 min exposure to each anesthetic and washout, pEPSP area increased to levels significantly more than control (P < 0.01-0.001). Exposure to a very small (0.025 MAC) concentration of isoflurane over the same period itself produced a similarly exaggerated pEPSP (P < 0.05) in the continued presence of the drug, suggesting that the phenomenon is a direct excitatory effect of the small concentrations of anesthetic on washout, unlike the true withdrawal observed with ethanol. Isoflurane, but not halothane, significantly increased the amount of potassium-stimulated release of the excitatory neurotransmitters glutamate, aspartate, and substance P, suggesting the hyperresponsiveness for that drug is the result of a presynaptically mediated increase in transmitter release. A broad spectrum specific protein kinase C inhibitor, GF109203X, blocked ethanol withdrawal hyperresponsiveness but not hyperresponsiveness after halothane. If the behavioral symptoms of emergence from anesthesia are based on excitatory actions similar to those observed in the spinal cord, the results show that they represent direct excitatory actions rather than withdrawal and are attributable to direct actions on ion channels or receptors, rather than indirect effects mediated by protein kinase C.
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PMID:Hyperresponsiveness on washout of volatile anesthetics from isolated spinal cord compared to withdrawal from ethanol. 1567 68

Environmental factors, such as adverse life experiences and family/peer influences have a substantial influence on the development of disorders related to alcohol use. In animals, maternal or peer separation/isolation has been used as an environmental intervention that has been shown to alter neurodevelopment and influence drinking behaviors in rodents and primates. In this study, the effects of adult peer isolation on subsequent ethanol intake were investigated in Wistar rats. Because central tachykinin levels have been reported to differ between rats selected for enhanced ethanol preference, neuropeptide [neurokinin A (NKA), substance P (SP)] concentrations were also estimated. Lower levels of ethanol intake, in a two-bottle free-choice model, were observed on the first day of forced ethanol drinking in the single-housed animals. However, overall ethanol consumption was unaffected by peer isolation. Peer isolation significantly lowered SP and NKA levels in the hypothalamus, but this effect was not related to ethanol consumption or body weight. These data indicate that endogenous SP and neurokinin levels are reduced by isolation housing, but this was not associated with alterations in drinking levels using a two-bottle choice procedure.
Alcohol 2005 Jun
PMID:Effect of social isolation on ethanol consumption and substance P/neurokinin expression in Wistar rats. 1639 42

The reinforcing properties of neuropeptides (substance P, corticoliberin, leu-enkephalin, alaptide) and 70 kDa heat shock protein (HSP) administered into the extended amygdala were studied on the hypothalamic self-stimulation model in rats reared in community or social isolation since the 17th day after birth. Since that time (17th day) half of rats were given 5 - 15 % ethanol solution instead of water (semiforced alcoholization). In the age of 90 - 100 days, all rats were implanted electrodes into lateral hypothalamus and cannulas into the central nucleus of amygdala. In the group of alcohol-dependent rats, the alcohol administration was continued. In rats reared in community, corticoliberin, leu-enkephalin and substance P increased the reinforcing properties of self-stimulation in dose-dependent manner, but alaptide and HSP decreased self-stimulation moderately. In rats reared in social isolation, the vector of neuropeptide effects was retained, although the magnitude of the effects was lower. Therefore, the neuropeptides differently participate in the reinforcing mechanisms of hypothalamus. It is suggested that the extended amygdala modulates the reinforcing properties of lateral hypothalamus, probably by means of extrahypothalamic corticoliberin-containing neurons.
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PMID:[Effect of peptides introduced into the central nucleus of amygdala on the hypothalamic self-stimulation in chronically alcoholized rats]. 1715 66

Intestinal inflammation is a painful syndrome with multiple symptoms, including chronic pain. This study examined the possible role of sensory neurons and substance P in symptoms of an animal model of acute intestinal inflammation. The model was induced by injecting ethanol and zymosan into the colon of anesthetized male rats. Three hours later, sections of the colon were stained with hematoxylin and eosin. To determine the role of substance P, 5 mg/kg of the neurokinin-1 receptor (NK-1r) antagonist, CP-96,345, or 300 microg/kg of an antisense oligonucleotide targeted at NK-1r mRNA was administered. Spinal cord sections were examined for internalization of NK-1r, as an indicator of substance P release. Sections of colon revealed infiltration of inflammatory cells following ethanol and zymosan treatment. Plasma extravasation in rats given ethanol and zymosan was significantly greater than in controls given saline only (P<0.0001) or saline and ethanol (P<0.001). In ethanol- and zymosan-treated rats given CP-96,345, plasma extravasation was significantly less than in rats given ethanol and zymosan without the antagonist (P<0.0001). Administration of the antisense oligonucleotide also resulted in lower levels of plasma extravasation compared with controls (P<0.01). Internalization of the NK-1r was observed in neurons of lamina I in the T13-L2 and L6-S2 regions of the spinal cord, as well as in sympathetic preganglionic neurons at the L1 level. This internalization was observed in the absence of any other stimulus besides the inflammation itself. This study implicates substance P and its receptor, the NK-1r, in acute inflammation of the colon.
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PMID:Sensory neuron and substance P involvement in symptoms of a zymosan-induced rat model of acute bowel inflammation. 1725 69

Capsaicin, a pungent constituent from red chilli peppers, activates sensory nerve fibres via transient receptor potential vanilloid receptors type 1 (TRPV1) to release neuropeptides like calcitonin gene-related peptide (CGRP) and substance P. Capsaicin-sensitive nerves are widely distributed in human and porcine vasculature. In this study, we examined the mechanism of capsaicin-induced relaxations, with special emphasis on the role of CGRP, using various pharmacological tools. Segments of human and porcine proximal and distal coronary arteries, as well as cranial arteries, were mounted in organ baths. Concentration response curves to capsaicin were constructed in the absence or presence of the CGRP receptor antagonist olcegepant (BIBN4096BS, 1 microM), the neurokinin NK1 receptor antagonist L-733060 (0.5 microM), the voltage-sensitive calcium channel blocker ruthenium red (100 microM), the TRPV1 receptor antagonist capsazepine (5 microM), the nitric oxide synthetase inhibitor Nomega-nitro-L-arginine methyl ester HCl (L-NAME; 100 microM), the gap junction blocker 18alpha-glycyrrhetinic acid (10 microM), as well as the RhoA kinase inhibitor Y-27632 (1 microM). Further, we also used the K+ channel inhibitors 4-aminopyridine (1 mM), charybdotoxin (0.5 microM) + apamin (0.1 microM) and iberiotoxin (0.5 microM) + apamin (0.1 microM). The role of the endothelium was assessed by endothelial denudation in distal coronary artery segments. In distal coronary artery segments, we also measured levels of cyclic adenosine monophosphate (cAMP) after exposure to capsaicin, and in human segments, we also assessed the amount of CGRP released in the organ bath fluid after exposure to capsaicin. Capsaicin evoked concentration-dependent relaxant responses in precontracted arteries, but none of the above-mentioned inhibitors did affect these relaxations. There was no increase in the cAMP levels after exposure to capsaicin, unlike after (exogenously administered) alpha-CGRP. Interestingly, there were significant increases in CGRP levels after exposure to vehicle (ethanol) as well as capsaicin, although this did not induce relaxant responses. In conclusion, the capsaicin-induced relaxations of the human and porcine distal coronary arteries are not mediated by CGRP, NK1, NO, vanilloid receptors, voltage-sensitive calcium channels, K+ channels or cAMP-mediated mechanisms. Therefore, these relaxant responses to capsaicin are likely to be attributed to a non-specific, CGRP-independent mechanism.
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PMID:Pharmacological characterisation of capsaicin-induced relaxations in human and porcine isolated arteries. 1729 25

Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to "negative" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)
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PMID:Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin. 1736 37

Although neurokinin 1 receptor antagonists prevent ethanol (EtOH)-induced gastric lesions, the mechanisms by which EtOH releases substance P (SP) and SP damages the mucosa are unknown. We hypothesized that EtOH activates transient receptor potential vanilloid 1 (TRPV1) on sensory nerves to release SP, which stimulates epithelial neurokinin 1 receptors to generate damaging reactive oxygen species (ROS). SP release was assayed in the mouse stomach, ROS were detected using dichlorofluorescein diacetate, and neurokinin 1 receptors were localized by immunofluorescence. EtOH-induced SP release was prevented by TRPV1 antagonism. High dose EtOH caused lesions, and TRPV1 or neurokinin 1 receptor antagonism and neurokinin 1 receptor deletion inhibited lesion formation. Coadministration of low, innocuous doses of EtOH and SP caused lesions by a TRPV1-independent but neurokinin 1 receptor-dependent process. EtOH, capsaicin, and SP stimulated generation of ROS by superficial gastric epithelial cells expressing neurokinin 1 receptors by a neurokinin 1 receptor-dependent mechanism. ROS scavengers prevented lesions induced by a high EtOH dose or a low EtOH dose plus SP. Gastric lesions are caused by an initial detrimental effect of EtOH, which is damaging only if associated with TRPV1 activation, SP release from sensory nerves, stimulation of neurokinin 1 receptors on epithelial cells, and ROS generation.
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PMID:Substance P released by TRPV1-expressing neurons produces reactive oxygen species that mediate ethanol-induced gastric injury. 1764 May 68

To understand the interactions between substance P and gut inflammation, changes in substance P levels were evaluated in a chronic model of ileitis in response to three anti-inflammatory agents with distinct mechanisms of action. The agents were the prostaglandin E(1) analogue misoprostol (30 mug/kg, s.c., b.i.d.), the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mug/ml in drinking water) and the leumedin, N-(fluorenyl-9-methoxycarbonyl)-L-leucine (NPC 15199, 10 mg/kg, s.c.). Ileitis was induced by a transmural injection of trinitrobenzene sulphonic acid (TNBS 30 mg/kg in 50% ethanol) into the distal ileum of guinea-pigs. All anti-inflammatory therapies were introduced after TNBS administration and continued until day 7, when guinea-pigs were killed. Ileal substance P levels were measured by radioimmunoassay, and granulocyte infiltration was quantified by myeloperoxidase (MPO) activity. Protein and nitrite (an index of nitric oxide formation) levels in a luminal saline lavage were quantified in all groups. TNBS ileitis caused a marked reduction in ileal substance P content and increased MPO activity, protein and nitrite secretion. The nitric oxide synthase inhibitor, L-NAME, completely restored all parameters to baseline. Misoprostol attenuated the granulocyte infiltration and exacerbated protein leak but had no effect on substance P levels. In contrast, NPC 15199 had no effect on granulocyte infiltration but normalized substance P levels and protein leak. Only L-NAME and NPC 15199 blocked the TNBS induced increase in nitrite levels. These results suggest that the regulation of granulocyte infiltration in this model is unrelated to changes in substance P levels. Inhibition of nitric oxide synthase was the most effective therapeutic strategy in TNBS ileitis but the precise interactions between nitric oxide and the enteric nervous system during inflammatory states remain to be defined.
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PMID:Anti-inflammatory agents and substance P depletion in experimental ileitis. 1847 36


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