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)

An active gelatinase has been purified from the conditioned medium of granulation tissue culture formed by carrageenin injection in rats. The purified gelatinase gave a single band corresponding to a M(r) of 57 kDa on both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and SDS-gelatin PAGE. The granulation tissue-derived gelatinase selectively cleaved the Gln6-Phe7 bond of substance P (SP) with a Km of 0.17 mM and a Vmax of 0.027 nmol SP7-11/min/micrograms protein, resulting in the generation of biologically inactive fragments, SP1-6 and SP7-11. Our data suggest that the gelatinase produced by granulation tissue participates in the inactivation of SP in the inflammatory site.
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PMID:Inactivation of substance P by granulation tissue-derived gelatinase. 128 Apr 34

Adult bovine articular chondrocytes were exposed to substance P, neurokinins A and B or substance P fragments, SP1-4, SP1-6 and SP7-11 in vitro. Proteoglycan synthesis was assessed by measuring proteoglycans which were released into the culture medium or incorporated into the cell layer. The intact tachykinins or substance P fragments had no direct effect on proteoglycan synthesis. Nor was total protein production affected. Gel chromatography, under dissociative conditions, revealed that sulphated proteoglycans detected in the medium or cell layer following treatment of chondrocytes with substance P, contained proteoglycans of similar molecular weight to those produced by cells exposed only to diluent controls. Therefore, we conclude that the acceleration of arthritis by substance P does not appear to be mediated through an effect on chondrocyte synthetic function.
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PMID:Failure of tachykinins including substance P and its fragments to influence proteoglycan and protein synthesis in bovine chondrocytes in vitro. 138 7

The presence of substance P in numerous mammalian pineal glands prompted us to search for its binding sites in the bovine pineal gland. The binding assays to pineal membrane were carried out in polypropylene microcentrifuge tubes in a final volume of 500 microliters of 50 mM Tris-HCl buffer (pH 7.4) containing aliquots of 200-500 micrograms protein, 0.02% BSA, 6 micrograms/ml chymostatin, 4 micrograms/ml leupeptin, 40 micrograms/ml bacitracin, 5 mM MnCl2, and 50 microliters of [3H]substance P (3H-SP, 45.7 Ci/mmol to yield a final concentration of 0.02-20 nM) to start the reactions, which were incubated for 20 min at 20 degrees C. The reactions were terminated by centrifugation in a Fisher Microcentrifuge Model 235A for 30 seconds at 13,000 X g, and the pellets were washed twice with 1 ml of ice-cold 50 mM Tris-HCl buffer containing 0.02% BSA, 6 micrograms/ml chymostatin, 4 micrograms/ml leupeptin, 40 micrograms/ml bacitracin, 5 mM MnCl2, 120 mM NaCl, 5 mM KCl, 1 mM MgCl2, and 1 mM CaCl2. The bottoms of the tubes were cut, the membrane pellets were dissolved in 5 ml of Triton X-100/toluene fluor (1:3) scintillation fluid, and the radioactivity was counted. The specific [3H]-substance P binding at 1-2 nM was 40-50% of the total binding, and the non-specific binding was assessed by using 2 microM of unlabelled substance P. These studies identified in bovine pineal gland a high affinity receptor site for [3H]SP with a KD value of 0.43 nM and a Bmax value of 71.14 fmol/mg protein. The relative affinity of various substance P analogues or fragments was: substance P greater than physalaemin greater than SP2-11 greater than SP3-11 greater than SP4-11 greater than SP6-11 greater than substance K = eledoisin greater than kassinin greater than SP7-11 greater than SP free acid. Substance P did not alter the basal or the norepinephrine-induced stimulation of the activity of serotonin N-acetyltransferase in rat pineal gland in culture.
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PMID:Studies on high-affinity [3H]substance P binding sites in bovine pineal gland. 243 Jul 88

A fraction enriched in neuronal growth cones isolated from developing rat forebrain was shown to possess binding sites for the substance P analog, Bolton-Hunter substance P [( 125I]BHSP). Specific binding of this ligand reached an equilibrium after 10 min at 20 degrees C, and was reversible and temperature-dependent. Removal of extracellular Na+ did not block but rather augmented [125I]BHSP binding suggesting that the labeled analog was not transported into the growth cone fraction. Scatchard analysis of the binding indicated a single class of non-interacting binding sites in the growth cone fraction (Kd: 257 pM; Bmax: 56 fmol/mg protein). From competition studies using substance P and other tachykinins, their rank order of potency for inhibiting [125I]BHSP binding was SP greater than physalaemin much greater than eledoisin greater than kassinin greater than NKB greater than or equal to NKA. Such order is consistent with the presence of an SP receptor (Neurokinin-1) in the growth cone fraction. The N-terminal fragments of substance P, SP1-7 and SP1-11 free acids, and the C-terminal fragment, SP7-11, were devoid of affinity for the [125I]BHSP binding site. However SP6-11 and SP1-11 methyl esters showed more potency.
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PMID:An isolated growth cone-enriched fraction from developing rat brain has substance P binding sites. 245 47

A search for low molecular weight peptide substrates for the metalloendoproteinase, human fibroblast stromelysin, resulted in the discovery that substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) is a substrate for this enzyme and is cleaved exclusively at the Gln6-Phe7 bond. On the basis of this observation, a semicontinuous HPLC-based assay was developed that monitors the production of the hydrolysis product, fragment 7-11 (SP7-11). Steady-state velocities for the production of SP7-11 have been determined as a function of substrate concentration and obey simple, Michaelis-Menten kinetics. For a 1-ml reaction volume, Vmax = (2.4 nmol SP7-11/min)/micrograms protein and Km = 0.38 mM.
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PMID:A semicontinuous, high-performance liquid chromatography-based assay for stromelysin. 247 83

Airway responses to rapid intravenous infusions of substance P (SP), selected carboxy terminal fragments (SP3-11, SP5-11, SP7-11, and SP9-11), and an amino terminal fragment (SP1-9) were measured in anesthetized, mechanically ventilated guinea pigs. The dose of each peptide required to decrease pulmonary conductance (GL) to 50% of baseline value was calculated in each animal. The order of ED50GL was: SP5-11 less than SP3-11 less than SP less than SP7-11. SP9-11 and SP1-9 were inactive at doses up to 1000 nmol/kg i.v. The effects of the neutral metalloendopeptidase (NEP) inhibitor, thiorphan, and the angiotensin converting enzyme (ACE) inhibitor, captopril, on airway responses to SP5-11 were examined in order to test the hypothesis that differences in degradation of SP and SP5-11 contribute to the difference in airway responsiveness to the two peptides. Thiorphan (0.5 mg/animal, i.v.) caused a significant decrease in ED50GL for SP5-11, as has been previously noted for SP. In contrast, captopril (1.7 mg/animal i.v.) had no effect on ED50GL for SP5-11, although it has a substantial effect on SP responses. These results indicate that while the carboxy terminal of SP is essential for peptide bronchoactivity, loss of amino terminal peptides (up to four residues) actually enhances bronchoconstrictor responses to the peptide. Part of this enhancement appears to result from differences in the degradation of SP and SP5-11 by ACE. The data suggest that cleavage of SP by dipeptidyl aminopeptidases could enhance its bioactivity.
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PMID:Airway responses to substance P and substance P fragments in the guinea pig. 248 79

Synthetic fragments and analogs were used to characterize specificity of antisera to SP and SP6-11. [Tyr8] SP and [Lys6] SP6-11 were both used as radioiodinated ligands. The latter was conjugated with Bolton-Hunter reagents before labelling. In both systems, the C-terminal pentapeptide SP7-11 was the shortest fragment showing antigenic identity with Substance P molecule. Substitution of different amino acid residues in SP6-11 by His or Gly showed that all but Glu6 take part in the structure of the antigenic determinant.
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PMID:Specificity of antisera obtained to substance P and its C-terminal hexapeptide. 257 23

Repetitive stimulation of the midbrain reticular formation with electrical stimuli causes extinction of the hippocampal theta rhythm. This phenomenon was used as an indicator of the effect of intracerebroventricular administration of the C-terminal hexapeptide substance P fragment (SP6-11), Leu- and Met-enkephalin on hippocampal electrical activity in the experiments performed on rabbits. Intracerebroventricular administration of SP6-11 caused an increase in the number of trains of pulses required to produce the extinction of the theta rhythm. Both of the enkephalins had opposite effects, the effect of Met-enkephalin being more than twice as strong as Leu-enkephalin. Control administration of C-terminal pentapeptide substance P fragment (SP7-11) and 0.9% NaCl solution had no significant effect on the tested phenomenon.
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PMID:Extinction of hippocampal theta rhythm evoked by mid-brain stimulation after intracerebroventricular administration of substance P fragment and enkephalin administration in rabbits. 617 Mar 89

Substance P (SP) and its COOH-terminal fragment (6-11) were coupled to bovine serum albumin by glutaraldehyde and used to elicit antibodies. Anti-SP and anti-SP6-11 antibodies bound to the same extent 125I-[Tyr8]-SP and 125I-[T-Lys6]-SP6-11. The latter was obtained after conjugation of the [Lys6]-SP6-11 with cold Bolton-Hunter reagent and then labelling by the chloramine-T method. In contrast to 125I-[Tyr8]-SP, 125I-[Tyr8]-SP6-11 was poorly bound by both anti-SP and anti-SP6-11 antibodies. Synthetic fragments of SP shorter than SP7-11 did not react with anti-SP6-11 antibodies. It is concluded that the antigenic determinant is within the COOH-terminal pentapeptide, and that Phe7, Phe8, Leu10 and Met11 contribute significantly to both anti-SP and anti-SP6-11 immunoreactivity.
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PMID:Immunogenic and antigenic properties of the COOH-terminal hexapeptide of substance P. 620 58

Rat chromaffin cells display phenotypic plasticity postnatally. In the presence of glucocorticoids, they retain a chromaffin cell phenotype, whilst in the presence of nerve growth factor and the absence of glucocorticoids they adopt a sympathetic neuronal phenotype. The tachykinins have some of the characteristics of a neurotrophic factor and are present in the form of a substance P afferent input in the rat adrenal medulla. We investigated the effects of stable NK1 and NK2 tachykinin receptor agonists, Ava[L-Pro,N-Me-Leu-10]SP7-11 (GR73632) and [Lys-3,Gly-8,R-Lac-Leu-9]NKA3-10 (GR64349), respectively, on the survival and phenotype of P5-7 rat chromaffin cells in vitro. GR73632 promoted neurite outgrowth, characteristic of the sympathetic neuronal phenotype, in the absence of NGF and glucocorticoids, but was without effect on survival after 2 weeks in culture. GR64349 was without effect.
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PMID:A selective tachykinin receptor agonist promotes differentiation but not survival of rat chromaffin cells in vitro. 768 Oct 11


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