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)

Doubly protonated substance P and two analogs alkylated at the ninth position was studied to determine the effect of N-alkylation of the amide nitrogen on the electrospray ionization/surface-induced dissociation (ESI/SID) fragmentation pattern. Thermal decomposition experiments and ab initio calculations were also used in conjunction with the ESI/SID experiments. The increase in relative abundances of the product ions resulting from the cleavage of the amide bond at the alkylation site (relative to the corresponding cleavage for substance P) can be explained by the increased basicity of the amide nitrogen in the context of the 'mobile proton' model. The relative abundances of singly charged b ions suggest a rearrangement of the amide hydrogen located N-terminal to the bond cleaved.
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PMID:Effect of alkyl substitution at the amide nitrogen on amide bond cleavage: electrospray ionization/surface-induced dissociation fragmentation of substance P and two alkylated analogs. 891 23

Exposure to nitrogen dioxide (NO2), a common oxidant airborne pollutant, has been shown to cause reversible effects on lung function and airway responsiveness, in addition to airways inflammation. However, there have been conflicting reports concerning NO2-induced airway hyperresponsiveness. In the present study, we investigated the isotonic smooth muscle response in isolated human bronchi previously exposed in vitro to NO2. Bronchial segments were obtained from 12 patients who had undergone thoracotomy for lung cancer. Bronchial segments from each patient were exposed to air and to 2.5 parts per million (ppm) NO2 for 4 h. The contractile response of bronchial rings to acetylcholine, neurokinin A (NKA), and substance P was then studied under isotonic conditions. The response to NKA was also studied in rings, with or without epithelium, exposed either to air or 7 ppm NO2. No NO2-induced alteration of the bronchial smooth muscle isotonic response was found under any of the experimental conditions. We conclude that in vitro exposure to up to 7 ppm nitrogen dioxide does not cause alterations of the human bronchial smooth muscle shortening capacity.
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PMID:Isotonic smooth muscle response in human bronchi exposed in vitro to nitrogen dioxide. 894 74

Crystal structures of nine non-peptide tachykinin NK1 antagonists have been analysed for the intermolecular interactions of their pharmacophoric groups with neighbouring molecules in the crystals. Experimental data on interaction geometries of these antagonists with their environment can be of help in understanding the mechanism of binding to the human NK1 receptor. Several interaction geometries have been identified that are consistent with both structure-activity relationships and reported receptor interactions for the compounds analysed. In addition, an interaction site for the side-chain of Gln-165 in the human NK1 receptor that is probably involved in donating a hydrogen bond to the benzylamino nitrogen or benzylether oxygen of the quinuclidine and piperidine antagonists is explicitly postulated. Also, a superposition based on pharmacophoric elements in the crystal structure conformations of two prototypic NK1 antagonists, CP-96,345 (1) and CP-99,994 (4), suggests how both compounds might interact with the human NK1 receptor in a similar manner.
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PMID:Possible ligand-receptor interactions for NK1 antagonists as observed in their crystal structures. 911 32

Annual nitrogen (N), phosphorus (P), and potassium (K) flows in agriculture in The Netherlands were identified and quantified in 1990, with special emphasis on pig production. Also, the effects that various management strategies in pig production have on NPK emission in 1990 were compared using a static deterministic simulation model. Ammonia emission from pig production in 1990 (60.9 Gg N) exceeded the defined target for the year 2000 (12.7 Gg N). Measures that affect volatilization of ammonia directly (i.e., introduction of low-emission stables, manure storage facilities, or manure application techniques) reduced ammonia emission most effectively. These measures, however, should be combined with a reduction in application of artificial N fertilizer to avoid an increase in N losses through leaching, run-off, or denitrification. Targets for ammonia emission in the year 2010 require a reduction in the pig population of 24 to 62%, in addition to implications of measures described in this article. National NPK losses in 1990 through leaching, run-off, or denitrification, predicted at 223.5 kg/ha for N, 32.7 kg/ha for P, and 67 kg/ha for K, exceeded government targets for the year 2010 (185 kg N/ha; 8.7 kg P/ha; norm not set for K). Reducing application of artificial NPK fertilizer reduced national NPK losses most effectively. For P, use of phytase and feeding pigs in accordance with their P requirements is required, in addition to limited use of artificial P fertilizer to meet targets for the year 2010. Hence, from an environmental point of view, pig production in The Netherlands is limited primarily by ammonia emission targets for the year 2010.
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PMID:Nutrient flows in agriculture in The Netherlands with special emphasis on pig production. 926 51

The effects of the nitric oxide (NO) synthesis inhibitor L-N5-(1-iminoethyl)-ornithine (L-NIO) on baseline tone and on responses to the endothelium-dependent vasodilator agents were investigated in the pulmonary vascular bed of the cat under constant-flow conditions. When administered in doses of 1 and 5 mg/kg i.v., L-NIO inhibited pulmonary vasodilator responses to acetylcholine, bradykinin, and substance P but did not alter vasodilator responses to adenosine, pinacidil, or adrenomedullin. L-NIO in doses of 1-10 mg/kg i.v. did not significantly affect baseline lobar arterial pressure, and when administered in doses of 10-30 mg/kg i.v. the inhibitory effect on responses to bradykinin and substance P was not greater than that observed when the lower doses of L-NIO were administered. L-NIO in doses of 5-30 mg/kg i.v. reduced plasma reactive nitrogen intermediate levels. The inhibitory effects of L-NIO were similar to the inhibitory effects of N omega-nitro-L-arginine, N omega-nitro-L-arginine methyl ester, and N omega-nitro-L-arginine benzyl ester. The highest dose of L-NIO studied (30 mg/kg i.v.) caused a significant increased in lobar arterial pressure, and the administration of N omega-nitro-L-arginine methyl ester (100 mg/kg i.v.) caused a significant increase in lobar arterial pressure in animals previously treated with L-NIO (1 mg/kg i.v.). The results of the present study show that the effects of L-NIO on endothelium-dependent vasodilator responses and on baseline tone can be separated and may be interpreted to suggest that basal release of NO does not play an important role in the maintenance of baseline tone in the pulmonary vascular bed of the cat.
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PMID:Differential effects of L-N5-(1-iminoethyl)-ornithine on tone and endothelium-dependent vasodilator responses. 931 93

Nitric oxide (NO) may regulate hepatic metabolism directly by causing alterations in hepatocellular (hepatocyte and Kupffer cell) metabolism and function or indirectly as a result of its vasodilator properties. Its release from the endothelium can be elicited by numerous autacoids such as histamine, vasoactive intestinal peptide, adenosine, ATP, 5-HT, substance P, bradykinin, and calcitonin gene-related peptide. In addition, NO may be released from the hepatic vascular endothelium, platelets, nerve endings, mast cells, and Kupffer cells as a response to various stimuli such as endotoxemia, ischemia-reperfusion injury, and circulatory shock. It is synthesized by nitric oxide synthase (NOS), which has three distinguishable isoforms: NOS-1 (ncNOS), a constitutive isoform originally isolated from neuronal sources; NOS-2 (iNOS), an inducible isoform that may generate large quantities of NO and may be induced in a variety of cell types throughout the body by the action of inflammatory stimuli such as tumor necrosis factor and interleukin (IL)-1 and -6; and NOS-3 (ecNOS), a constitutive isoform originally located in endothelial cells. Another basis for differentiation between the constitutive and inducible enzymes is the requirement for calcium binding to calmodulin in the former. NO is vulnerable to a plethora of biologic reactions, the most important being those involving higher nitrogen oxides (NO2-), nitrosothiol, and nitrosyl iron-cysteine complexes, the products of which (for example, peroxynitrite), are believed to be highly cytotoxic. The ability of NO to react with iron complexes renders the cytochrome P450 series of microsomal enzymes natural targets for inhibition by NO. It is believed that this mechanism provides negative feedback control of NO synthesis. In addition, NO may regulate prostaglandin synthesis because the cyclooxygenases are other hem-containing enzymes. It may also be possible that NO-induced release of IL-1 inhibits cytochrome P450 production, which ultimately renders the liver less resistant to trauma. It is believed that Kupffer cells are the main source of NO during endotoxemic shock and that selective inhibition of this stimulation may have future beneficial therapeutic implications. NO release in small quantities may be beneficial because it has been shown to decrease tumor cell growth and levels of prostaglandin E2 and F2 alpha (proinflammatory products) and to increase protein synthesis and DNA-repair enzymes in isolated hepatocytes. NO may possess both cytoprotective and cytotoxic properties depending on the amount and the isoform of NOS by which it is produced. The mechanisms by which these properties are regulated are important in the maintenance of whole body homeostasis and remain to be elucidated.
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PMID:The role of nitric oxide in hepatic metabolism. 959 11

Methodology was developed that uses reverse phase, high performance liquid chromatography (HPLC) to identify and quantify bradykinin, substance P, and neurokinin A contained in dental pulp tissue. Pulp tissue was prepared and homogenized from teeth frozen in liquid nitrogen, Known amounts of three substances found in inflamed tissue were added to the homogenized tissue and also to bovine serum albumin (BSA) (positive control), and supernatants were analyzed using HPLC. Other pulp tissue was prepared and analyzed without the addition of the substances. Recovery from the pulp and BSA with added substances was similar, with bradykinin recovered maximally. In pulp tissue without additions, all three substances were recovered. Thus HPLC appears to be a viable alternative to other methods for identification of these substances and allows for their quantification.
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PMID:Identification of bradykinin, substance P, and neurokinin A in human dental pulp. 959 64

The health effect of atmospheric pollution is causing increasing public concern. Several controlled human-exposure studies have clearly. shown that oxidant pollutants, including ozone, nitrogen dioxide, and diesel exhaust, induce an acute inflammatory response in human airways. The main component of this response involves the influx of polymorphonuclear leukocytes (PMN) and is mediated via the upregulation of transcription factors NF-kappa B, AP-1, and NF-IL6; leukocyte-endothelial adhesion molecules, and chemokine secretion, including IL-8 and Gro-alpha. The results of recent studies also suggest that short-term exposure to ozone leads to neurogenic inflammation by causing damage to the bronchial epithelium and stimulating subepithelial sensory nerves to release substance P. In addition, such exposures lead to the consumption of endogenous antioxidants that are present in the airway lining fluid. Studies in asthmatics have shown that oxidant pollutants, including ozone and nitrogen dioxide, induce PMN influx in the airways and potentiate responses to inhaled aero-allergens. This article will review various studies addressing the toxicological mechanisms underlying oxidant pollutant-induced airways injury.
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PMID:Toxicological mechanisms underlying oxidant pollutant-induced airway injury. 971 22

We investigated whether acute exposure to nitrogen dioxide (NO2) causes major inflammatory responses (inflammatory cell recruitment, oedema and smooth muscle hyperresponsiveness) in guinea pig airways. Anaesthetised guinea pigs were exposed to 18 ppm NO2 or air for 4 h through a tracheal cannula. Bronchoalveolar lavage was performed and airway microvascular permeability and in vitro bronchial smooth muscle responsiveness were measured. Exposure to NO2 induced a significant increase in eosinophils and neutrophils in bronchoalveolar lavage fluid, microvascular leakage in the trachea and main bronchi (but not in peripheral airways), and a significant in vitro hyperresponsiveness to acetylcholine, electrical field stimulation, and neurokinin A, but not to histamine. Thus, this study shows that in vivo exposure to high concentrations of NO2 induces major inflammatory responses in guinea pig airways that mimic acute bronchitis induced by exposure to irritant gases in man.
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PMID:Bronchopulmonary inflammation and airway smooth muscle hyperresponsiveness induced by nitrogen dioxide in guinea pigs. 1042 65

It is known that substance P acts as a vasodilator via activation of the enzyme nitrogen monoxide synthase (NOS) in endothelial tissue and it is suggested that N-methyl-D-aspartate (NMDA) could stimulate nitrogen monoxide (NO) release within nervous tissue. However, the data reported concern NO metabolites (nitrites, nitrates), while there is no clear evidence to date of the action of the latter compound within the aortic tissue. In this study, amperometry with specifically prepared carbon fiber electrodes has been applied to examine the effect of NMDA or substance P upon NO release. In particular, the data obtained confirm that NMDA can stimulate NO release in vivo, in the striatum of anaesthetized rats, and that substance P can stimulate NO release in rat aortic rings (ex vivo experiments). In addition, they indicate that NMDA also stimulates NO release in rat aortic rings. This original data has been confirmed by the observation of a vasorelaxant action of NMDA within noradrenaline precontracted aortic rings. Thus, these experiments provide the first direct evidence that NMDA can mediate vascular relaxation via NO release.
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PMID:Voltammetric and functional evidence that N-methyl-D-aspartate and substance P mediate rat vascular relaxation via nitrogen monoxide release. 1086 34


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