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)

A highly sensitive and specific radioimmunoassay for somatostatin has been used to study inactivation of the neurohormone by plasma and hypothalamic peptidase(s). Specificity of the inactivation process was indicated by the absence of interference by addition of luteinizing hormone releasing hormone, thyrotropin-releasing hormone, oxytocin, or substance P. The inactivating ability of hypothalamic tissue and plasma was destroyed by heating and the protease inhibitor benzamidine prevented plasma activity, thus suggesting the enzymatic nature of the processes involved. The present data suggest that the inactivation of somatostatin by hypothalamus and plasma could be an important factor in the regulation of circulating somatostatin levels.
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PMID:Enzymatic degradation of somatostatin by rat plasma and hypothalamus. 70 24

In human cerebrospinal fluid, aminopeptidase, dipeptidyl aminopeptidase, dipeptidyl carboxypeptidase, and carboxypeptidase which were capable of hydrolyzing enkephalins were detected. Among these enzymes, two distinct aminopeptidase, designated C-AP1 and C-AP2, were partially purified. These enzymes were not purified thoroughly, but the characteristics of C-AP2 were similar to those of an aminopeptidase purified from monkey brain. But the inhibitory activity of amastatin on C-AP2 was stronger, and that of substance P was negligible. On the other hand, characteristics of C-Ap1 were extremely differ from those of C-AP2 or an aminopeptidase purified from monkey brain. C-AP1 had an optimum pH more in the acidic range (the highest at pH 6.0) and was not inhibited by any of the protease inhibitor tested including bestatin and amastatin.
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PMID:Partial purification of two distinct enkephalin-degrading aminopeptidases from human cerebrospinal fluid. 240 80

From rat brain, a membrane bound substance P-degrading endopeptidase (SPE) was purified 1580 fold to near homogeneity. After extraction with 10 mM CHAPS, the enzyme preparation was subjected to ion exchange chromatography on DEAE-cellulose, adsorption chromatography on hydroxyapatite, gelfiltration through Ultrogel AcA 44 and FPLC on Mono Q. This enzyme of 70,000 molecular weight is optimally active at pH 7.5. Metal chelators (EDTA and EGTA) and sulfhydryl modifying reagents (N-ethylmaleimide and p-chloromercuriphenylsulfonic acid) are strongly inhibitory while the serine-protease inhibitor diisopropyl-fluorophosphate does not effect the enzyme activity. The enzyme is strongly inhibited by bacitracin but not by phosphoramidon and captopril. Degradation of substance P is strongly inhibited by neurotensin, somatostatin, ACTH 1-39, and less effectively by LHRH but not by Leucine-enkephalin. Substance P is preferentially hydrolyzed at the Gln6-Phe7 peptide bond but fragmentation at the Pro4-Gln5, Gln5-Gln6,Phe7-Phe8 and Gly9-Leu10 bonds was also observed.
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PMID:A membrane bound substance P degrading endopeptidase from rat brain. 244 28

The effect of substance P (SP) and other tachykinins on respiratory glycoconjugate (RGC) release was studied in a feline tracheal organ culture system. SP in concentrations of 10(-5) and 10(-6) M stimulated an increase in RGC release of 35 +/- 8% and 18.5 +/- 5%, respectively. The addition of the protease inhibitor aprotinin or the enkephalinase inhibitor thiorphan to the cultures had no effect on the baseline secretion of RGC but markedly potentiated the activity of SP. SP in the presence of aprotinin or thiorphan was active at 10(-8) -10(-9) M concentrations and was more potent at each concentration studied (in the presence of peptidase inhibitors). Among other tachykinins studied, only physalaemin in the presence of aprotinin had a clear stimulatory effect on RGC release at 10(-6) M concentration (26% +/- 5% increase above control, n = 4, p less than 0.02); kassinin, neurokinin A, and neurokinin B had little or no effect on RGC secretion in concentrations of 10(-6) M or less. Autoradiographic studies of [125I]SP binding revealed SP receptor expression in the submucosal glands of the feline trachea. [125I]SP binding was inhibited in the presence of excess unlabeled SP. We conclude that SP receptors are present in the feline tracheal submucosal glands and that binding to SP receptors results in RGC secretion.
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PMID:Substance P receptor-mediated secretion of respiratory glycoconjugate from feline airways in vitro. 246 45

The effect of substance P (SP) on the cardiodynamics of the isolated working rat heart perparation was examined. The peptide over the concentration range of 10(-8) to 10(-6) M was found to have no influence on aortic pressure, cardiac output, or cardiac work. However, a 10-15% reduction in coronary flow was observed at 1 x 10(-6) M substance P. Octapeptide substance P (SP4-11) exhibited a similar vasoconstrictive action. The IC50 of SP4-11 was 2 x 10(-13) M compared to an IC50 of 3.5 x 10(-8) M for substance P. Perfusion of the heart in the presence of bacitracin (1 x 10(-4) M), a protease inhibitor, prevented the reduction in coronary flow observed in the presence of substance P. By contrast, the reduction in coronary flow produced by octapeptide substance P was not altered by the presence of bacitracin. Thus, it appears that a C-terminal fragment such as SP4-11 may be responsible for the observed decrease in coronary flow.
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PMID:Action of substance P on the working rat heart. 618 69

1. Experiments were designed to study the effects of ageing on muscarine and NK2 receptor mechanisms in the three different regions of rabbit airway. 2. The pD2 value of acetylcholine changed with age in three different regions while that of carbamylcholine, which is resistant to acetylcholinesterase, did not. 3. The pD2 values of neurokinin A and the activity of protease, a degradative enzyme, changed with age. However, by the pretreatment with phosphoramidon, a protease inhibitor, the regional difference and age related change of the pD2 value of neurokinin A disappeared. 4. In conclusion, the observations about age related changes and regional differences of pD2 value of acetylcholine and neurokinin A were due to the difference of their degradative enzyme activities.
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PMID:Effects of ageing on regional differences in the contractile responses to acetylcholine and neurokinin A in rabbit airway. 795 29

Using pharmacologic agents, we explored the mechanism by which a potent neuropeptide, substance P, induces the secretion of histamine from human skin mast cells and compared their effects on substance P-induced histamine release to the secretion activated by anti-IgE. Histamine release from human cutaneous mast cells induced by substance P was inhibited by the Ge-protein inhibitor pertussis toxin that, in turn, did not affect the IgE-mediated secretion. Similarly to anti-IgE, two activators of protein kinase C, tetradecanoylphorbol acetate (TPA) and bryostatin 1, significantly inhibited the substance P-induced response. In contrast, drugs that enhance intracellular levels of cAMP, an inhibitor of protein kinases, genistein, and a protease inhibitor, AEBSF, did not affect substance P-induced histamine secretion, whereas these compounds significantly reduced the response initiated by anti-IgE. Our data demonstrate that substance P activates human cutaneous mast cells by acting on G proteins and protein kinase C. Our results also suggest that the biochemical pathways underlying mast cell activation by substance P and anti-IgE are to a great extent unrelated.
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PMID:Substance P activates the release of histamine from human skin mast cells through a pertussis toxin-sensitive and protein kinase C-dependent mechanism. 880 44

The new chromatographic system Akta-Purifier 10 (Amersham-Pharmacia Biotech), scaled for preparative HPLC, was used for the purification of Substance P (SP) endopeptidase activity in the ventral tegemental area (VTA) of the rat brain. SP endopeptidase previously identified and purified from human cerebrospinal fluid has been found to degrade the neuroactive peptide SP in a specific pattern. In this study we have recovered SP endopeptidase from the rat VTA following a purification scheme involving homogenization (ultrasonication) and extraction of the excised tissue, size-exclusion chromatography (Superdex 75 HR), and ion-exchange chromatography (Resource Q). In this way we were able to achieve a purification factor of almost 7,500, based on specific activity. The obtained SP endopeptidase activity, was then subjected to characterization with regard to inhibition profile. The enzyme activity was monitored by following the conversion of SP to its N-terminal fragment SP(1-7) using a radioimmunoassay, specific for the heptapeptide product. On basis of inhibition profile it was possible to discern two different SP endopeptidase-like activities, one sensitive toward the protease inhibitor phosphoramidon (preparation A), and another non-sensitive to phosphoramidon or captopril (preparation B). The molecular masses of preparations A and B, as derived from sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were found to be 90,000 and 76,000, respectively. Our data suggest that the purified phosphoramidon sensitive endopeptidase activity may be an enzyme that plays a major role in the conversion of SP to its bioactive fragment SP(1-7) in the rat VTA. This is likely to be identical to the previously known neutral endopeptidase (EC 3.4.24.11). However, this study also demonstrates the existence of a distinct endopeptidase activity with properties in agreement with rat spinal cord SP endopeptidase. In the context of previously shown altered levels of SP(1-7) in the VTA during morphine withdrawal both purified enzyme activities may turn out to be responsible.
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PMID:Purification of substance P endopeptidase activity in the rat ventral tegemental area with the Akta-Purifier chromatographic system. 1104 91

Inflammatory bladder disorders such as interstitial cystitis (IC) deserve attention since a major problem of the disease is diagnosis. IC affects millions of women and is characterized by severe pain, increased frequency of micturition, and chronic inflammation. Characterizing the molecular fingerprint (gene profile) of IC will help elucidate the mechanisms involved and suggest further approaches for therapeutic intervention. Therefore, in the present study we used established animal models of cystitis to determine the time course of bladder inflammatory responses to antigen, Escherichia coli lipopolysaccharide (LPS), and substance P (SP) by morphological analysis and cDNA microarrays. The specific aim of the present study was to compare bladder inflammatory responses to antigen, LPS, and SP by morphological analysis and cDNA microarray profiling to determine whether bladder responses to inflammation elicit a specific universal gene expression response regardless of the stimulating agent. During acute bladder inflammation, there was a predominant infiltrate of polymorphonuclear neutrophils into the bladder. Time-course studies identified early, intermediate, and late genes that were commonly up-regulated by all three stimuli. These genes included: phosphodiesterase 1C, cAMP-dependent protein kinase, iNOS, beta-NGF, proenkephalin B and orphanin, corticotrophin-releasing factor (CRF) R, estrogen R, PAI2, and protease inhibitor 17, NFkB p105, c-fos, fos-B, basic transcription factors, and cytoskeleton and motility proteins. Another cluster indicated genes that were commonly down-regulated by all three stimuli and included HSF2, NF-kappa B p65, ICE, IGF-II and FGF-7, MMP2, MMP14, and presenilin 2. Furthermore, we determined gene profiles that identify the transition between acute and chronic inflammation. During chronic inflammation, the urinary bladder presented a predominance of monocyte/macrophage infiltrate and a concomitant increase in the expression of the following genes: 5-HT 1c, 5-HTR7, beta 2 adrenergic receptor, c-Fgr, collagen 10 alpha 1, mast cell factor, melanocyte-specific gene 2, neural cell adhesion molecule 2, potassium inwardly-rectifying channel, prostaglandin F receptor, and RXR-beta cis-11-retinoic acid receptor. We conclude that microarray analysis of genes expressed in the bladder during experimental inflammation may be predictive of outcome. Further characterization of the inflammation-induced gene expression profiles obtained here may identify novel biomarkers and shed light into the etiology of cystitis.
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PMID:Gene expression profiling of mouse bladder inflammatory responses to LPS, substance P, and antigen-stimulation. 1205 14

In the present study the existence of a non-AT(1), non-AT(2) angiotensin (Ang) binding site unmasked by the organomercurial protease inhibitor p-chloromercuribenzoate (PCMB) was demonstrated in mouse brain membranes, consistent with observations previously reported in the rat (Karamyan and Speth, 2007b). The pharmacological specificity of the non-AT(1), non-AT(2) angiotensin binding site was similar to the rat brain: Sar(1)-Ile(8)-Ang II > Ang III >or= Ang II > Ang I> p-aminophenylalanine(6) Ang II> CGP42112 >> Ang IV > Ang 1-7 congruent with shorter angiotensin fragments. Neurotensin, bradykinin, and luteinizing hormone-releasing hormone showed K(i) values >10 microM, while substance P and VIP had K(i) values of approximately 2 microM. The non-AT(1), non-AT(2) angiotensin binding site was not present in adrenal, liver or kidney. Subcellular fractionation showed a higher density of [(125)I]Ang II binding in plasma membrane (P2) fractions of cerebral cortex and hypothalamus relative to debris (P1) fractions. The binding site is present in the brains of mice in which the AT(1a), AT(1b), AT(2), Mas, and neprilysin (EC 3.4.24.11, neutral endopeptidase) was knocked out confirming that the binding site is not a heretofore described angiotensin receptor or neprilysin. These observations confirm that this novel Ang binding site is distinct from classical AT(1), AT(2), AT(4) and Ang 1-7 receptors while retaining a high specificity for angiotensins that act on the known angiotensin receptors. Whether this binding site functions as a novel receptor for angiotensins or a specific angiotensinase with variable functionality at different redox states will require further study.
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PMID:Characterization of the brain-specific non-AT(1), non-AT(2) angiotensin binding site in the mouse. 1857 43


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