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)

Histamine H1-antagonists inhibit the weal-and-flare responses to the intradermal injection of platelet activating factor (PAF) in humans, and PAF response is reduced in histamine-depleted skin sites. This indicates that mast cell histamine release is likely to be the mechanism of this response. We have therefore studied the interaction of PAF with cutaneous mast cells by observing whether it releases histamine directly from human dispersed foreskin mast cells, potentiates the activity of known mast cell stimulants or liberates histamine releasing factors (HRFs) from human platelets and leucocytes to release mast cell histamine by an indirect mechanism. At a concentration of 100 microM both PAF C18 and PAF C16 caused near maximal release (83.5 +/- 4.3% and 88.2 +/- 4.5% respectively) of the total histamine content of the cell. This release was not inhibited in the absence of extracellular Ca2+, by the lack of metabolic energy or in the presence of the PAF antagonists WEB 2086 (100 nM-3 microM) or BN 52021 (100 nM-10 microM). These results indicate a cytotoxic mechanism of histamine release by PAF 100 microM. PAF (10 nM-1 microM) failed to potentiate the mast cell-stimulating activity of anti-IgE, calcium ionophore A23187 or substance P and it did not induce the release of HRFs for skin mast cells when incubated with platelets and leucocytes in concentrations up to 1 microM.
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PMID:Platelet activating factor does not release histamine from human dispersed cutaneous mast cells. 169 68

Chemical derivatization by phenylglyoxal (PGX) was applied to the identification of arginine in the neuropeptides dynorphin A (1-6) and substance P. The obtained products were separated on a short reversed phase C18 column and analysed on-line with the photodiode array UV technique. The selective attachment of a chromogenic molecule into the arginine residue resulted in significant change in the absorbance spectra around 250 nm, depending on the number of PGX molecules attracted. Further analysis employed fast atom bombardment mass spectrometry (FAB MS) and C-terminal sequencing for detailed verification of the derivatives formed during modification with PGX. The results clearly demonstrated that the photodiode array technique, when combined with chemical modification of certain amino acids, provides new possibilities for the analysis of peptide structures.
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PMID:Application of photodiode array detection and fast atom bombardment mass spectrometry for the identification of the arginine residue in neuropeptides. 172 24

Neurokinin A and B (NKA and NKB) and neuropeptide K (NPK) were recently isolated from porcine spinal cord and brain, and together with substance P (SP) considerably extend the list of tachykinin-like peptides present in the mammalian nervous system. In order to investigate the distribution of tachykinins in the central nervous system (CNS) we have recently developed sensitive radioimmunoassays (RIA) for both SP and NKA. As NKB and NPK cross-react in the RIA for NKA we were able to determine the content of NKA, NKB and NPK after separation of rat CNS extracts by reverse-phase high-performance liquid chromatography (HPLC). Comparison of different extraction methods suggested that 0.1 M hydrochloric acid gave the best extraction and recovery of NKA-like immunoreactivity from rat brain. Characterization of these tachykinins using HPLC and gel-filtration columns revealed that C18 columns did not adequately separate NPK from NKB under the conditions used by previous authors. Thus 'NKB' content reported previously on the basis of HPLC separation would correspond to the sum of both NPK and NKB content. In the present study, therefore, we introduced modified elution conditions to resolve NPK from NKB and determined the regional distributions of these tachykinins in the rat CNS. SP was the most abundant tachykinin in every region studied. After SP, the NKA concentration was highest and NKB concentration was lowest in all regions except for the cortex and hippocampus where the NPK concentration was highest. The molar ratio of these peptides seemed to be relatively constant in the 3 regional groups (striatum-substantia nigra, cerebral cortex-hippocampus, dorsal root ganglia-dorsal and ventral horns of spinal cord) and suggests that regional specific translation or processing may exist.
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PMID:Regional distribution of neuropeptide K and other tachykinins (neurokinin A, neurokinin B and substance P) in rat central nervous system. 243 60

Levels of substance P (sP), peptide-histidine-isoleucine (PHI), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), neurotensin (NT), bombesin (BOM) and methionine-enkephalin (Met-Enk) like immunoreactivity were measured in cat, dog, primate and sloth cervical, thoracic, lumbar and sacral dorsal and ventral horns and dorsal root ganglia. The levels of peptides in the cat sacral cord and the principal peaks of immunoreactivity on a 10-60% acetonitrile gradient on a C18 reverse phase high performance liquid chromatography (HPLC) were sP (sP1-11: 369 ng/g), PHI (PHI: 271 ng/g), VIP (VIP1-28: 210 ng/g), Met-Enk (Met1-5 and extended forms: 257 ng/g), BOM (BOM1-10 and GRP1-27: 20 ng/g), CCK (CCK-8: 15 ng/g) and NT (NT1-13: 10 ng/g). Consideration of the rostrocaudal levels revealed an approximately even distribution with the exception of VIP and PHI which showed sacral/cervical ratios of 79 and 63. For sP, Met-Enk and BOM dorsal/ventral ratios were greater than 1 at all spinal levels. For VIP, PHI and CCK these ratios were greater than 1 only in the sacral cord. Dorsal root ganglion (DRG) levels of sP, VIP, PHI were readily measurable in single ganglia and covaried with the respective levels in the dorsal cord. Pooled samples of spinal ganglia and the trigeminal ganglia revealed that the relative levels of peptide immunoreactivity were: sP (25 ng/g); VIP (26 ng/g); PHI (28 ng/g); Met-Enk (6 ng/g); CCK (2 ng/g); NT (1 ng/g); and BOM (1 ng/g).
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PMID:Survey of distribution of substance P, vasoactive intestinal polypeptide, cholecystokinin, neurotensin, Met-enkephalin, bombesin and PHI in the spinal cord of cat, dog, sloth and monkey. 245 58

125I[D-Ala2, Met5] enkephalin with high specific activity (122-185 Ci/mmol) was prepared and purified by Sep-Pak C18 reverse phase cartridge followed by high performance liquid chromatography (HPLC). HPLC at pH 3.0 resolved 125I[D-Ala2, Met5] enkephalin into two fractions, which ran as a single spot in thin-layer chromatography with the same Rf values. Alkaline hydrolysates of the HPLC-purified fractions showed a single spot corresponding to monoiodotyrosine standard when analysed by thin-layer chromatography. Binding kinetics of the tracer was found to approach equilibrium after 30 min at 24 degrees. Scatchard analysis of the saturation equilibrium binding studies gave an equilibrium dissociation constant of 3.58 nM and the number of binding site of 30 fmol/mg protein. Enkephalin analogs were capable of displacing 125I[D-Ala2, Met5] enkephalin binding from the rat brain plasma membrane. The effective concentration of [D-Ala2, Met5] enkephalin and [D-Ala2, Leu5] enkephalin for 50% inhibition of 125I[D-Ala2, Met5] enkephalin binding was estimated to be 79 nM and 23 nM, respectively. Both substance P and gastrin tetrapeptide failed to displace the 125I[D-Ala2, Met5] enkephalin binding to any significant extent. The 125I[D-Ala2, Met5] enkephalin prepared by the present procedure is therefore a useful tracer. This method of preparing radioiodinated peptide may be applicable to other enkephalin analogs or neuropeptides in general.
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PMID:Radioiodinated [D-Ala2, Met5] enkephalin. Preparation, purification by high performance liquid chromatography and binding characteristics. 609 38

A coordinated series of immunohistochemical and biochemical analyses have been conducted in the hamster to examine the dependence of substance P and tyrosine hydroxylase (TH) expression by second-order olfactory neurons, and the level of dopamine in the main olfactory bulb (MOB), on the integrity of carnosine- and olfactory marker protein (OMP)-containing primary afferent neurons. Substance P-like immunoreactivity (SPLI) is localized in external tufted cells and centrifugal afferents of the MOB; TH immunoreactivity has a wider distribution, in external tufted, middle tufted, periglomerular, and deep short-axon cells as well as in centrifugal afferents. To characterize the SPLI, this material was isolated by guanidine-HCl extraction and passage over a C18 SEP-PAK. The SPLI coelutes on HPLC with authentic substance P and, following oxidation, coelutes with substance P sulfoxide. It is sensitive to alpha-chymotrypsin and is resistant to trypsin. Thus, the SPLI in the MOB behaves as authentic substance P. Intranasal irrigation with 0.17 M ZnSO4 results in peripheral deafferentiation of the MOB for up to 8 months as evidenced by a persistent loss of OMP immunoreactivity and shrinkage of the olfactory nerve layer and glomeruli. By these criteria, the vomeronasal inputs to the accessory olfactory bulb are not destroyed and the spared vomeronasal receptor neurons do not innervate the vacated peripheral projection field in the MOB. The loss of peripheral inputs to the MOB is accompanied by marked and parallel reductions in the incidences of SPLI- and TH-positive second-order neurons despite an increase in the density of neuronal somata in the glomerular layer. Biochemical quantifications following peripheral deafferentation also demonstrate significant decreases of both substance P and dopamine, together with the expected decrease of carnosine. In contrast, the SPLI and the TH and serotoninlike immunoreactivities in centrifugal afferents as well as the TH immunoreactivity in deep interneurons do not appear to be reduced, and the MOB content of norepinephrine in centrifugal afferents is unaffected. These results collectively indicate that the loss of inputs from the primary olfactory receptor neurons can reduce the levels of at least two different, putatively neuroactive compounds (substance P and dopamine) in at least three classes of second-order neurons (external tufted, middle tufted, and periglomerular cells). The control of central neuron phenotype by the peripheral olfactory neurons thus appears to be a phenomenon of broad influence. It may play a role in processing chemosensory information as well as offering a system in which to study neuronal plasticit
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PMID:Substance P and catecholaminergic expression in neurons of the hamster main olfactory bulb. 619 81

Physalaemin (Mr = 1284) is a potent undecapeptide from the skin of South American frogs. The amino acid sequence of the COOH-terminal region of this peptide is similar to that of substance P. An antiserum specific for the NH2-terminal sequence of physalaemin enabled the quantitation and localization of physalaemin-like immunoreactivity (PSLI) in mammalian tissues. PSLI is found in acid extracts of whole trachea from rat, rabbit, and guinea pig and in the tracheal mucosal layer in the dog, cow, and pig. The concentration determined by radioimmunoassay ranged from 1 to 15 ng/g dry weight of tissue, with rat trachea containing the highest amount. Gel filtration of an extract of rabbit trachea on Bio-Gel P-4 revealed a single peak of immunoreactivity that had an approximate Mr of 1700, similar to that detected in extracts of guinea pig and rabbit stomach. In contrast to amphibian physalaemin, mammalian PSLI 1) has a higher molecular weight, 2) is resistant to alpha-chymotrypsin or trypsin digestion, 3) elutes earlier from a C18 alkylsilane resin with increasing concentrations of methanol, and 4) can be separated from physalaemin by thin-layer chromatography. These data indicate that the mammalian PSLI is different in structure from the amphibian peptide.
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PMID:A substance with immunoreactivity to the peptide physalaemin in mammalian respiratory tissue. 716 58

The recoveries of substance P (SP) and five related peptides were evaluated on different types of solid-phase extraction sorbent. Best results were obtained by use of a C18 silica gel cartridge. Marked differences of extraction yields occurred for the different peptide fragments and, in general, recovery increased with increasing hydrophobicity of the peptide when reversed-phase materials like C18 and C8 cartridges were used. This observation is indicative of a sorption-desorption mechanism by prevailing solvophobic interactions. A similar trend was found when phenylpropyl silica gel (CPhenyl), generally known as a reversed-phase adsorbent of lower hydrophobicity, was used. It was concluded that a substantial participation of analyte-matrix pi-pi interactions has to be taken into account when extraction yields are compared with corresponding values obtained by use of a C8 cartridge. With CN silica gel cartridges, marked differences in extraction yields were obtained by use of acetonitrile or methanol as the organic modifier. As an attempt to explain this observation, conformational effects were assumed for the sorption-desorption behaviour of the peptides on the polar matrix.
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PMID:Recovery of substance P and related C-terminal fragments on solid-phase extraction cartridges for subsequent high-performance liquid chromatographic separation and radioimmunoassay. 768 Oct 69

CAM 4515 and CAM 4750 are new nonpeptide tachykinin NK1 receptor antagonists with different lipophilicities. Two separate, simple, and sensitive HPLC methods for the quantitation of these two compounds in plasma and the evaluation of their oral bioavailability in rats were developed and validated. Extraction of CAM 4515 from plasma involved protein precipitation with acetonitrile, while that for CAM 4750 involved a one-step liquid-liquid extraction with methylene chloride. The analytes in extracts were chromatographed on a C18 column using two different separation buffers, 47% 0.02 M sodium citrate (pH 3.5)-53% acetonitrile for CAM 4515 and 59% 0.02 M potassium phosphate dibasic (pH 7.0)-41% acetonitrile for CAM 4750, and both compounds were detected by fluorescence (excitation 278 nm; emission 342 nm). Stability profiles of both drugs at -20 degrees C or room temperature in plasma and in reconstituted buffers were good. The limit of quantitation for both drugs was 5 ng ml-1 with good linearity from 5 to 1000 ng ml-1 using 100-200 microliters of plasma. Excellent precision (relative standard deviation < 8.3%) and accuracy (relative error +/- 9.2%) were observed for both CAM 4515 and CAM 4750. Oral bioavailability studies were conducted for each compound in rats receiving a p.o. dose of 20 mg kg-1 and an i.v. dose of 5 mg kg-1. The absolute oral bioavailability of CAM 4750 (80%) was estimated to be 40-fold greater than that of CAM 4515 (2%). The experimental results suggest that incorporation of a pyridine group into the structural backbone may greatly improve bioavailability.
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PMID:Development of HPLC plasma assays for CAM 4515 and CAM 4750, two new nonpeptide tachykinin antagonists, and application to bioavailability studies. 888 18

CAM 5500 and CAM 5187 are new nonpeptide tachykinin NK3 receptor antagonists with different lipophilicity and solubility. We have developed and validated two separate, simple HPLC methods for quantitation of these two compounds in plasma to support oral pharmacokinetic/bioavailability studies in rats. The two compounds in plasma were extracted on cyano SPE cartridges with different washing schemes to optimize extraction efficiency and chromatographic specificity. The analytes and internal standard in the resulting extracts were chromatographed on a C18 HPLC column, using mobile phases containing different phosphate buffer strengths and acetonitrile concentrations. Both compounds were detected using UV, Peak area ratios were proportional over the concentration range of 50-3000 ng ml-1 for CAM 5500, and 100-1500 ng ml-1 for CAM 5187. Stability profiles of both drugs and internal standard in rat plasma at 37 degrees C and in injection solvent at ambient temperature were good. Assay precision, based on quality controls, was < 5.6% and 13.4% (%RSD) for CAM 5500 and CAM 5187, respectively. Similarly, assay accuracy for both compounds was within +/- 7.1% and +/- 6.0% (%RE), respectively. The HPLC methods were successfully applied to assay samples from two oral bioavailability studies. Oral bioavailability studies were conducted for each compound in rats receiving a PO dose of 20 mg kg-1 or an i.v. dose of 5 mg kg-1. Despite their difference in lipophilicity and solubility, the absolute oral bioavailability of CAM 5500 (5.3 +/- 4.8%) is similar to that of CAM 5187 (8.8% +/-3.2%).
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PMID:Development and application of sensitive HPLC assays for NK3 antagonists in rat plasma. 957 34


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