Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenously released cyclooxygenase products modulate the bronchoconstrictor response to various stimuli in asthma. Little is known of the change in airway responsiveness to neurokinin A (NKA) after cyclooxygenase blockade. In this randomized, double-blind, placebo-controlled study, we have investigated the effect of the potent cyclooxygenase inhibitor, lysine acetylsalicylate (L-ASA) administered by inhalation, on the bronchoconstrictor response both to neurokinin A (NKA) and methacholine in nine asthmatic subjects. Subjects attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg.mL-1) or matched placebo (glycine, solution of 30 mg.mL-1) 15 min prior to bronchial challenge with NKA or methacholine, in a randomized, double-blind order. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1) and agonist responsiveness, expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). L-ASA elicited a significant fall in FEV1 from baseline. When compared with placebo, inhaled L-ASA reduced the airway responsiveness to NKA in 8 of the 9 subjects studied, the geometric mean (range) values for PC20 NKA increasing significantly from 153.2 (52.0-258.9) to 303.1 (83.4-668.5) micrograms.mL-1 after placebo and L-ASA, respectively. However, no significant change in airway responsiveness to methacholine was recorded after L-ASA, their geometric mean (range) PC20 values being 1.60 (0.17-9.59) and 1.53 (0.09-14.01) mg.mL-1 after placebo and L-ASA, respectively. The small decrease in airway responsiveness to neurokinin A after administration of lysine acetylsalicylate by inhalation suggests that endogenous prostaglandins may play a contributory protective role in the airway response to neurokinin A in human asthma.
 ...
PMID:Changes in neurokinin A airway responsiveness with inhaled lysine-acetylsalicylate in asthma. 880 29

LC-high-resolution electrospray ionization (ESI)-MS data for a number of bioactive peptides, including substance P and bradykinins were acquired over a wide mass range by scanning the magnetic sector and calibrating externally with polyethylene glycol standards. Multiply charged ions were observed and errors between observed and theoretical monoisotopic molecular masses were typically in the 5 to 30 ppm range for the peptides during LC-ESI-MS and ESI-MS operation with magnetic sector resolutions between 2500 and 6000 (10% valley definition). Under collisionally activated dissociation conditions bn- and yn-series sequence ions were generally observed, enabling amino acid sequencing and the differentiation of lysine from glutamine, two amino acids differing in residue mass by only 0.0364 u. Mass accuracy was evaluated during an international round robin analytical exercise where the molecular masses of five unknown peptides were to be accurately determined. Isotopic clusters for charge states of up to +6 were fully resolved, facilitating the rapid and unambiguous assignment of charge states and calculation of monoisotopic molecular masses. Errors between theoretical and observed monoisotopic molecular masses were in the 2 to 18 ppm range for the five unknown peptides.
 ...
PMID:Analysis of bioactive peptides by liquid chromatography-high-resolution electrospray mass spectrometry. 917 6

Extracts from ragweed pollen grains contain novel trypsin and chymotrypsin-like serine peptidases which are described in this report. The molecular mass of the chymotrypsin-like enzyme was 82 kDa, had a pH optimum near 9.0, and its activity was unaffected by chelating or reducing agents. It was inhibited by diisopropyl fluorophosphate (DFP), a general serine class inhibitor, and more specifically N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a chymotrypsin-like proteinase inhibitor. In addition to various synthetic substrates, the neuropeptides, vasoactive intestinal peptide (VIP) and substance P, which are required for normalized lung functions, were also rapidly hydrolysed. Activity toward protein substrates was not detected with the exception of the inactivation of alpha-1-proteinase inhibitor (alpha-1-PI) which occurred through cleavage within the reactive site loop. The 'trypsin-like' enzyme has a molecular mass near 80 kDa, a blocked N-terminus, a pH optimum near 9.0, and requires Ca++ for stability and activity, but not reducing agents. It is inhibited by DFP, and more specifically the trypsin-like proteinase inhibitor, N-p-tosyl-L-lysine chloromethyl ketone (TLCK). Again, activity toward protein substrates was not detected, but various synthetic substrates and biologically active peptides were efficiently cleaved. Significantly, atrial natriuretic peptide (ANP) and angiotensin 2 (ATII), whose degradation would amplify kinin activity and influence inflammatory diseases of the respiratory tract and nasal passages, were also rapidly hydrolyzed.
 ...
PMID:Ragweed pollen proteolytic enzymes: possible roles in allergies and asthma. 946 75

Many extracellular matrix molecules are expressed in the embryonic nervous system and there is some evidence that they are important regulators of neural development. Of these molecules, laminin appears to be the most potent, affecting virtually all neurons of the peripheral and central nervous system. This study was undertaken to investigate the effects of laminin on the proliferation and differentiation of cultured neuroepithelial cells taken from fetal rat forebrains (embryonic day 17-19). The results are summarized as follows. 1) Neuroepithelial cells cultivated in epidermal growth factors containing serum-free medium subsequently differentiated into neurons, astrocytes, and oligodendrocytes. 2) Neuronal cells derived from neuroepithelial cells were immunoreactive for gamma-aminobutyric acid (GABA) or substance P, but were not for serotonin and tyrosine hydroxylase. 3) In western blot analysis, the phosphorylated neurofilament content in neuronal cells was higher in culture on laminin than in culture on poly-L-lysine (PLL). 4) The proliferation rate of GABAergic neurons was higher in culture on laminin than in culture on PLL. These results suggest that GABAergic and substance P-ergic neurons can be differentiated from neuroepithelial cells and that laminin promotes the differentiation of neuronal cells from neuroepithelial cells and the increased proliferation rate of GABAergic cells.
 ...
PMID:The effects of laminin on the characteristics and differentiation of neuronal cells from epidermal growth factor-responsive neuroepithelial cells. 958 53

A method for labeling proteins and peptides with (methoxycarbonyl cyclopentadienyl)tricarbonyl rhenium and technetium is described. The precursors used for this labeling are conveniently produced from perrhenate and pertechnetate, respectively, using a double ligand transfer reaction. For labeling the lysine residues of the model protein bovine serum albumin, the technetium methyl ester was saponified and then transformed into its N-hydroxysuccinimidyl ester. For the labeling of the model peptides leucine enkephalin, substance P, oxytocin, and the tumor imaging/therapy candidate octreotide, the rhenium methyl ester was saponified and activated using either 1-hydoxybenzotriazole or 1-hydroxy-7-azabenzotriazole. The activation and peptide-coupling reactions were followed using reversed-phase (C18) HPLC and yields averaged approximately 70%.
 ...
PMID:Protein and peptide labeling with (cyclopentadienyl)tricarbonyl rhenium and technetium. 981 71

This paper describes the development of analytical methodology for the separation of naphthalene-2,3-dicarboxaldehyde (NDA)-derivatized substance P (CBI-SP) and five lysine-containing metabolites by micellar electrokinetic chromatography (MEKC). The effect of surfactant composition and organic modifiers on the separation was investigated. The final separation buffer consisted of 80 mM sodium cholate in 50 mM N-tris (hydroxymethyl)methyl-2-aminoethanesulfonic acid (TES), pH 7. All six lysine-containing peptides were separated under these conditions.
 ...
PMID:Separation of naphthalene-2,3-dicarboxaldehyde-derivatized-substance P and its metabolites by micellar electrokinetic chromatography. 1087 58

The non-enzymatic production of a protein-bound adduct by the action of the acyl adenylate of bile acids is described. On incubation of deoxycholyl adenylate with substance P in phosphate buffer, peptides covalently bound with one or two molecules of the bile acid were detected. The modified peptides were structurally characterized by time-of-flight mass spectrometry with matrix-assisted laser desorption/ionization (MALDI-TOFMS) in the post-source decay mode, and by liquid chromatography/electrospray ionization MS/MS. The deoxycholic acid was bound on substance P through the amino group at Arg-1 and/or Lys-3. The adenylate of cholic acid also produced the protein-bound bile acid on incubation with lysozyme, and the binding sites of the cholic acid appeared to be the lysine residues at 1, 33, 97 and 116. The results clearly suggest that bile acid adenylates in vivo may act as active intermediates to produce covalently bound bile acid adducts with peptides and proteins by nucleophilic displacement of the 5'-adenylic acid through the free amino groups.
 ...
PMID:Bile acid acyl adenylate: a possible intermediate to produce a protein-bound bile acid. 1118 May 37

Short peptides with sequences derived from those found in the tegumental antigen of Fasciola hepatica have been synthesised. Incubation of some of these peptides with rat peritoneal mast cells resulted in the degranulation of the cells as measured by a histamine release assay. This activity was shown to be associated with the proline-lysine-proline motif, which is responsible for the induction of mast cell degranulation by the mammalian bioactive peptide substance P. Studies on the mode of action of the fluke-derived peptide indicated that it was operating through the same biochemical pathways as substance P. The implications of these findings for the development of immune responses during parasite infections are discussed.
 ...
PMID:Liver fluke (Fasciola hepatica)-derived peptides activate rat peritoneal mast cells. 1275 46

The decapeptide kallidin-10, substance P and angiotensin increased the resistance of guinea-pig lungs to inflation; lysine- or arginine-vasopressin and oxytocin were inactive. Acetylsalicylate antagonized this action of kallidin-10, as it does that of bradykinin, but it failed to antagonize substance P or angiotensin. Bradykinin also increased resistance to inflation of rabbit lungs and, to a lesser extent, rat lungs. It caused a relatively slow contraction of guinea-pig tracheal and bronchial muscle in vitro, but it did not contract isolated rabbit, dog or human bronchus. The relative potencies of different substances on different bronchial test preparations, and also in different species, were not parallel.
 ...
PMID:Actions of some peptides on bronchial muscle. 1386 45

Substance P is readily expressed in skin inflammatory disorders such as psoriasis and contact dermatitis. Spantide II is a peptide (MW 1668.76) that specifically binds to neurokinin-1 receptor (NKR-1) and blocks inflammation associated with substance P. The anti-inflammatory property of Spantide II makes it a suitable candidate to be studied as a topical formulation for the treatment of dermal inflammatory disorders. The objective of this study was to investigate the influence of pH, temperature, salt concentration and concentration on the aqueous stability of Spantide II. The stability of Spantide II was also assessed by circular dichroic (CD) spectroscopy and mass spectrometry (MS). The influence of various dermatological vehicles (ethanol, Transcutol, propylene glycol, N-methyl-2-pyrrolidone (NMP), ethyl oleate, isopropyl myristate and laurogylcol FCC (LFCC)) on the stability of Spantide II was investigated. A precise high-performance liquid chromatography (HPLC) assay was developed for analysis of Spantide II. At higher temperature (40 degrees C) the stability of Spantide II decreased with increase in pH (P < 0.05). Change in salt concentration did not appreciably affect the stability of Spantide II (P > 0.05). The concentration of Spantide II in the solution had no significant influence on its stability (P > 0.05). CD spectroscopy studies showed that Spantide II has a relatively stable alpha-helix structure in the liquid state. The stability of Spantide II was affected by the type of vehicle used in the study (P < 0.01) at different temperatures (P < 0.05). Spantide II at high temperature undergoes lysine-proline diketopiperazine degradation as evident in MS data. Spantide II was relatively more stable in ethyl oleate-ethanol, ethanol-water, ethanol and N-methyl-2-pyrrolidone. The results of this study indicate that ethyl oleate-ethanol (1:1) and ethanol-water (1:1) could be used as potential vehicles in the development of topical formulations of Spantide II.
 ...
PMID:Preformulation stability of Spantide II, a promising topical anti-inflammatory agent for the treatment of psoriasis and contact dermatitis. 1497 97


<< Previous 1 2 3 4 5 6 7 Next >>