UNIPROT:P20366 - FACTA Search

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 presence of substance P (SP) in the amniotic fluid (AF) from 88 obstetric patients was determined with a radioimmunoassay. AF was collected from each patient in EDTA-coated tubes. Cross-reactivity of anti-SP antibody with methionine, met-enkephalin, leu-enkephalin, beta-endorphin, eledoisen and physalemin was less than 1%. The SP levels during the midtrimester were not significantly lower than those of late gestation. Data on the late-gestation group were evaluated further as per the clinical problem. The only statistically significant finding was between the diabetics with fetal maturity and the non-diabetic group. This preliminary study identified the presence of SP in AF in mid and late gestation.
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PMID:Amniotic fluid levels of substance P. 127 66

The aim of this study was to describe the normal distribution of calcitonin gene-related peptide (CGRP) and substance P (SP) containing fibres in the knee joint of the mouse and to obtain insight into the changes in innervation associated with degenerative processes in the joint. Arthrosis was induced by a single subpatellar intra-articular injection of bacterial collagenase. After decalcification in EDTA solutions, the CGRP and SP fibres were visualized by peroxidase-antiperoxidase pre-embedding immunocytochemistry for light microscopy. Control experiments on the mouse brain as a reference for the effect of EDTA on the immunostaining showed that the decalcification procedure with EDTA had not impaired the immunostaining. A rich innervation of thin varicose CGRP and SP immunoreactive fibres was found in most peri- and intra-articular tissue components. The periosteum, synovial tissues, the joint capsule and the intra-articular fat tissues were richly innervated. Less intense innervations were also found in the subchondral bone plates of the tibio-femoral joint and of the patella. Fibres were also found in the soft tissues between the patellar tendon and the femoral groove. No differences could be found between the location of CGRP and SP fibres with respect to the localization in the joint, but generally more CGRP fibres were found. The collagenase-induced osteoarthrosis was characterized by sclerosis of the subchondral bone, patellar dislocation, osteophyte formation, synovial proliferation and by severe cartilage abrasion, particularly on the medial side of the femoro-tibial joint. The overall distribution of CGRP and SP fibres was the same as in the control joints. However, major differences were found in all studied joints at specific locations around the cruciate ligaments, in the synovium around the patella, in the soft tissues lateral of the patella and in plica tissue between the patella and femoral groove. The CGRP and SP innervation was no longer detectable by immunolabelling with the antibodies. With a polyclonal antibody to the growth associated protein GAP-43/B-50, signs of degenerated axonal profiles were observed in these locations. At other peripheral locations, such as the muscles, the GAP-43/B-50 distribution was normal. In conclusion, the present study provides detailed information on the localization of CGRP and SP fibres, which may be involved in pain perception. Knowledge of the changes that occur during arthrosis may give more insight into the clinical symptoms.
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PMID:Calcitonin gene-related peptide, substance P and GAP-43/B-50 immunoreactivity in the normal and arthrotic knee joint of the mouse. 128 63

Aminopeptidase P (EC 3.4.11.9) was purified from rat brain cytosol. A subunit Mr of 71,000 was determined for the reduced, denaturated protein whereas an Mr of 143,000 was determined for the native enzyme. The purified aminopeptidase P selectively liberated all unblocked, preferentially basic or hydrophobic ultimate amino acids from di-, tri- and oligopeptides with N-terminal Xaa-Pro- sequences. Corresponding peptides with penultimate Ala instead of Pro were cleaved with much lower rates; oligopeptides with residues other than Pro or Ala in the penultimate position appeared not to be substrates for the enzyme. Several bioactive peptides with Xaa-Pro sequences, especially bradykinin, substance P, corticortropin-like intermediate lobe peptide, casomorphin and [Tyr]melanostatin were shortened by the N-terminal amino acid by aminopeptidase P action. Rat brain aminopeptidase P was optimally active at pH 7.6-8.0 in the presence of Mn2+. Chelating agents and SH-reacting reagents inhibited the enzyme, but common inhibitors of aminopeptidases, like amastatin or bestatin, of prolidase or of dipeptidyl peptidases II and IV, like N-benzoyloxycarbonyl-proline or epsilon-benzyl-oxycarbonyl-lysyl-proline, as well as antibiotics like beta-lactam ones, bacitracin or puromycin, had little or no effect.
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PMID:Aminopeptidase P from rat brain. Purification and action on bioactive peptides. 164 59

To investigate the functional heterogeneity of mouse mast cells, we extracted and purified cutaneous and peritoneal mast cells from 10- to 18-week-old BALB/c mice and compared their responses to secretagogues. Cutaneous mast cells (CMC) were extracted from mouse ears after digestion with hyaluronidase and collagenase in MEM containing 25% fetal calf serum and purified on a discontinuous Percoll gradient. The histamine content of cells obtained from the 30/40% interface was 1.0 +/- 0.1 pg/cell (mean +/- SE), with a mast-cell purity of 68.6 +/- 4.4% and a viability of greater than 93%. Peritoneal mast cells (PMC) were obtained by lavage with modified Tyrode's buffer followed by purification on 22.5% and 3-9% metrizamide gradients. The histamine content of cells was 12.2 +/- 0.8 pg/cell, with a mast-cell purity of 95.9 +/- 0.6% and a viability of greater than 95%. Histamine release induced by A23187 from CMC peaked at 3.0 microM A23187 (19.1 +/- 4.2%), at 3.0 min (22.3 +/- 2.3%), and at 30 degrees C (17.6 +/- 2.6%). In contrast, histamine release from PMC peaked at 8.0 microM of A23187 (49.4 +/- 12.1%) and at 15.0 min (48.5 +/- 12.2%). Release of histamine from PMC was observed at all the temperatures tested from 22 to 45 degrees C. Histamine release from CMC and PMC induced by A23187 was calcium dependent. Histamine release induced by compound 48/80 from CMC peaked at 0.5 micrograms/ml of compound 48/80 (23.0 +/- 7.4%) and at 5.0 min incubation (16.3 +/- 2.0%), whereas release from PMC peaked at 10.0 micrograms/ml (31.9 +/- 2.6%); release from PMC was similar at all the time points examined (1-15 min). Histamine release induced by substance P (SP) from both CMC and PMC peaked at 5.0 microM (18.8 +/- 6.6% and 12.6 +/- 3.7%, respectively); however, the maximal release from CMC occurred at 3.0 min (18.2 +/- 3.2%) and from PMC at 30.0 min (11.4 +/- 2.0%). SP-induced histamine release from CMC was calcium dependent, whereas release from PMC was only partially inhibited by EDTA. This study demonstrated that functional heterogeneity exists between these two populations of mast cells.
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PMID:Mast-cell heterogeneity: functional comparison of purified mouse cutaneous and peritoneal mast cells. 169

The sea urchin hatching enzyme (HEz) is a protease capable of dissolving the fertilization envelope that surrounds the embryo as a protective coat during early development. We have now purified a 37-kDa active enzyme from the supernatant fluid of hatched blastula medium of the species Hemicentrotus pulcherrimus. The purified enzyme was completely inhibited by alpha 2-macroglobulin and the chelating agents EDTA, EGTA, and 1,10-phenanthroline and was slightly inhibited by chymostatin and pepstatin, but was not inhibited by various other serine and thiol protease inhibitors. These results suggest that HEz is a metalloproteinase. Quantitative analyses of the products of HEz's action on various peptides revealed that the enzyme preferentially cleaved the peptide bonds on the amino side of bulky hydrophobic residues, -Leu, -Ile, and -Phe as well as -Tyr, in a similar but more limited fashion than thermolysin. Furthermore, although substance P was a good substrate of HEz, snake venom alpha-protease, and thermolysin, the analogue [Sar9]substance P was a poor substrate for HEz. This analogue was a good substrate for thermolysin and alpha-protease, but the scissile bonds were altered from those of substance P. The failure of HEz and alpha-protease to cleave the P1-P1 bond that meets the primary specificity is ascribed to the presence of an imino acid residue (proline or sarcosine) or the absence of any amino acid at the P2h or P3' position, in contrast to the simple P2' restriction of thermolysin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The specificity of sea urchin hatching enzyme (envelysin) places it in the mammalian matrix metalloproteinase family. 171 95

Neurotensin (NT) endopeptidase (EC 3.4.24.16) has been purified about 800-fold from pig brain by four sequential chromatographic steps depending on ion-exchange and hydrophobic interactions. Two types of preparation were studied: one from a Triton X-100-solubilized membrane fraction, and the other from the soluble fraction containing 90% or more of the total activity in the homogenate. NT endopeptidase activity was monitored by high-precision liquid chromatography of the two peptide products, characterized as NT-(1-10) and NT-(1-8), resulting from cleavage of the Pro10-Tyr11 and Arg8-Arg9 bonds respectively. As purification proceeded, from both membranes and cytosol, the yield of the two products achieved a constant ratio of 5:1 and this ratio was reproduced in repeated purifications. However, a distinct peptidase which hydrolysed exclusively at the Arg8-Arg9 bond was partially resolved from NT endopeptidase by chromatography on hydroxyapatite, and this activity was further purified and assigned to endopeptidase-24.15 (EC 3.4.24.15). SDS/PAGE of both preparations of neurotensin endopeptidase revealed a major band of apparent Mr 75000, and treatment of the membrane-associated form with N-Glycanase gave no evidence that the enzyme was a glycoprotein. The membrane-associated and cytosol forms of NT endopeptidase activities, monitored for both NT-(1-10) and NT-(1-8) products, were compared in their responses to 1,10-phenanthroline, EDTA, dithiothreitol (DTT) and some synthetic site-directed inhibitors of endopeptidase-24.15 or peptidyl dipeptidase A. The effects revealed no significant differences between the two preparations, nor did the reagents discriminate between the activities generating the two NT fragments. The partially purified form of endopeptidase-24.15 was also included in this comparison: while some responses were similar, this peptidase was distinguishable in its activation by DTT and its relative resistance to inhibition by EDTA. Both forms of NT endopeptidase were found to hydrolyse other substrates, including Boc-Phe-Ala-Ala-Phe-4-aminobenzoate, bradykinin and substance P (these at faster rates than neurotensin), as well as dynorphin A-(1-8) and luliberin. The bonds hydrolysed in these neuropeptides, as well as in angiotensins I and II and alpha-neoendorphin, were defined. These studies confirm that NT endopeptidase is distinct from endopeptidase-24.15. They further show that the former is a soluble enzyme, not an integral membrane protein, that it is not peptide-specific and that it might be more appropriately named. enzyme, not an integral membrane protein, that it is not peptide-specific and
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PMID:Purification and properties of a neurotensin-degrading endopeptidase from pig brain. 190 21

Dispersed canine antral mucosal cells were prepared by sequential steps of collagenase digestion and EDTA treatment. Cell preparations enriched in gastrin cells were made by centrifugal elutriation followed by step density gradient centrifugation. Specific, saturable, and reversible binding of 125I-[Tyr4]-bombesin was found in all preparations. This saturable binding was time, temperature, and cell number dependent. In both velocity (elutriator) and density cell separation experiments, saturable binding of bombesin correlated with the distribution of cells containing gastrin- but not somatostatin-like immunoreactivity. Maximal specific binding to gastrin (G) cell-enriched fractions was reached in 45 min at 37 degrees C and constituted 90% of total binding. Addition of 100 nM nonradioactive bombesin to cells incubated with 50 pM 125I-[Tyr4]-bombesin for 45 min resulted in time-dependent dissociation of specifically bound tracer to about 40% of the maximal equilibrium binding. Analysis of saturable equilibrium binding yielded a best fit to a one-site model of high affinity binding sites with an apparent Kd of 85 +/- 14 pM and a Bmax of 231,000 +/- 71,000 receptors/gastrin cell. Nonradioactive [Tyr4]-bombesin and related analogs inhibited the specific binding of the tracer in a dose-related manner. The rank order of potency, determined at the IC50, of [Tyr4]-bombesin and related analogs for inhibition of specific binding was bombesin greater than [Tyr4]-bombesin = hGRP-27 greater than GRP-10 greater than ranatensin much greater than neuromedin B. Cholecystokinin, somatostatin, substance K, and kassinin each tested at a concentration of 1 microM did not inhibit bombesin binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of bombesin receptors on canine antral gastrin cells. 197 73

Cells of the N-18 line of mouse neuroblastoma and their membrane degrade substance P added exogenously. The degradation by the cells and their membrane, examined by high-performance liquid chromatography, is strongly inhibited by EDTA but scarcely inhibited by captopril and phosphoramidon. Gly-Leu-Met-NH2 is the major cleavage product among C-terminal fragments of substance P in both cases. Thus, the degradation of substance P by the neuroblastoma cells and their membrane seems to take place mainly through the hydrolysis between Phe8-Gly9 by EDTA-sensitive protease(s).
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PMID:Degradation of substance P by the neuroblastoma cells and their membrane. 240 67

Metabolites of substance P, produced by incubation with isolated epithelial cells and with purified brush border and basolateral membrane from pig small intestine, were isolated by high performance liquid chromatography and identified by amino acid analysis. Rapid cleavages between Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10 and oxidation of the methionine residue at position 11 were observed with cells and with both membrane fractions. Formation of substance P3-11' indicative of the action of dipeptidylaminopeptidase IV (EC 3.4.14.5), was observed only at high substrate concentration. Proteolytic degradation was inhibited by phosphoramidon and by EDTA but was insensitive to chloride ion concentration and to captopril. These observations suggest that inactivation of substance P in the epithelial layer of the gut is mediated through endopeptidase-24.11 (EC 3.4.24.11) in the cell-surface membrane and that degradation by angiotensin-converting enzyme (EC 3.4.15.1), although present in high concentration in the mucosa, is unimportant.
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PMID:Proteolytic inactivation of substance P in the epithelial layer of the intestine. 241 32

Hydrolysis of substance P and nine kinds of substance P analogs by angiotensin-converting enzyme highly purified from rat lung was examined by using amino-group fluorometry and high-performance liquid chromatography. The enzyme hydrolyzed substance P and several analogs, notwithstanding that they did not contain free C-terminal residues. The analyses of cleavage products separated by high-performance liquid chromatography indicated that the enzyme hydrolyzed substance P and its analogs mainly at the bond between Phe8-Gly9 and also at another bond, possibly between Gly9-Leu10, to a lesser extent by an endopeptidase action, followed by successive release of dipeptides by a dipeptidyl carboxypeptidase action. The analogs that had D-amino acid residues substituted at the presumed cleavage sites were scarcely hydrolyzed. It was further found that (Pyr6)-fragment (6-11) was hydrolyzed by the enzyme more efficiently than the other fragment-type analogs and was cleaved at a single bond by the endopeptidase activity of the enzyme. Therefore, this fragment was used as a substrate in order to characterized the endopeptidase activity of the enzyme by employing fluorometry. The activity was dependent on chloride ion, and was inhibited by captopril, MK-421, and EDTA. Thus, the endopeptidase activity of the enzyme showed properties similar to those of the dipeptidyl carboxypeptidase activity of the enzyme.
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PMID:Hydrolysis of substance P and its analogs by angiotensin-converting enzyme from rat lung. Characterization of endopeptidase activity of the enzyme. 241 12

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