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 peptidase activity of rat diencephalon membranes, which acts on the C-terminal hexapeptide sequence of substance P, was characterized using the radiolabeled substrate N alpha-[( 125I]iododesaminotyrosyl)-substance P (6-11)-hexapeptide. This activity presents certain characteristics similar to those of the substance-P-degrading enzyme purified from human brain by Lee et al. [Eur. J. Biochem. 114, 315-327 (1981)]. It is inhibited by metal chelators and some thiol reagents, but is insensitive to inhibitors of serine proteases and aminopeptidases. The activity is different from angiotensin-converting enzyme and enkephalinase, since it is not affected by specific inhibitors of these enzymes. Substance P and substance P C-terminal fragments longer than the pentapeptide inhibited the degradation of the radiolabeled substrate with inhibition constants around 200 microM. Short fragments of the substance P sequence, such as Boc-Phe-Phe-OMe and Boc-Phe-Phe-Gly-OEt, were also found to inhibit the degradation of the substrate. When the metal-chelating hydroxamic acid moiety was attached to the carboxyl terminus of these short peptides, potent inhibitors of the substance-P-degrading activity were obtained, with inhibition constants in the micromolar range. The most potent of these compounds, iododesaminotyrosyl-Phe-Phe-Gly-NHOH (IBH-Phe-Phe-Gly-NHOH), is a competitive inhibitor, with a Ki value of 1.9 microM. The degradation of substance P by rat diencephalon slices was inhibited to the same extent (40-50%) by IBH-Phe-Phe-Gly-NHOH (20 microM) and by phosphoramidon (1 microM). A combination of both reagents reduced the degradation rate by 75-80%, suggesting that both enkephalinase and the substance-P-degrading activity are involved in the metabolism of substance P in this preparation. IBH-Phe-Phe-Gly-NHOH seems to be quite specific for the latter enzyme, since at a high concentration (0.1 mM) it did not affect the degradation of the radiolabeled substrate by alpha-chymotrypsin, papain, or thermolysin.
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PMID:Inhibition of substance P degradation in rat brain preparations by peptide hydroxamic acids. 241 Feb 67

Antisera generated to substance P-Gly (SP-G) and substance P-Gly-Lys (SP-G-K), the likely unamidated COOH-terminally extended forms of substance P, were used to quantify and localize substance P precursor forms in hamster brain stem and spinal cord. The precursor determinant SP-G-K was liberated from larger heterogeneous forms by mild trypsinization of tissue extracts and was converted into the second precursor determinant, SP-G, by subsequent treatment with carboxypeptidase B. The basal levels of SP-G-K in brain stem and spinal cord were approximately equal to 0.5 pg/mg of tissue and rose 43- to 64-fold after trypsinization. Basal levels of SP-G were comparable to those of SP-G-K and rose 10- to 29-fold after combined enzyme treatments. Immunohistochemical labeling of axons and somata with anti-SP-G-K increased dramatically after trypsinization. This labeling was eliminated by preadsorption with authentic SP-G-K but not substance P or SP-G. Gel-permeation chromatography revealed SP-G-K-like immunoreactivity in fractions corresponding to considerably higher molecular weight than mature substance P. Collectively, these results support the hypothesis that substance P is synthesized from larger precursors and demonstrate that extended precursor forms are normally present in the axons and somata of neural systems that synthesize substance P.
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PMID:Precursor forms of substance P (SP) in nervous tissue: detection with antisera to SP, SP-Gly, and SP-Gly-Lys. 241 Sep 6

[Adpoc-Glu(N3)6, (Met-N3)11] substance P-(6-11)-peptide was reacted with diamines H2N(CH2) nNH2 (n = 3-10, 12) to give cyclopeptides. Subsequent careful cleavage of the Adpoc group leads to the formation of compounds of type cyclo-[H-Glu-Phe-Phe-Gly-Leu-Met-NH-(CH2) n-NH-] X HCl. The substances produce a specific two-phase myotropic effect in experiments on isolated guinea pig ileum. The compounds where n is 3, 7, 12 exhibit also a hypotensive activity when assayed on anaesthetized rats.
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PMID:[Substance P. New cyclic analogs]. 241 37

Substance P (SP) and other tachykinins altered the potential differences (P.D.) and resistances (omega) of open-circuited epithelial preparations. (1) The effects observed were critically dependent on the side to which the peptides were added. Luminal addition of SP (5 x 10(-7) M) produced within 8-20 s, a rapid decrease in P.D. (dip) followed by an increase that peaked transiently and declined. Serosal addition led to an increase in P.D. after a longer lag (40-90 s). In both cases, resistance decreased. (2) Low concentrations of SP (5 x 10(-12) M) elicited only an increase in P.D., the dip appearing at concentrations 50-100-fold higher, indicating perhaps receptors with different affinities. (3) Changes in P.D. and resistance were seen on luminal addition of physalaemin, eledoisin, kassinin, alpha-neurokinin, neuromedin K and C-terminal SP fragments larger than 5 amino acids. No responses were seen with SP tetrapeptide, SP 9-11, bombesin, litorin, neurotensin, dynorphin. The sequence Phe-X-Gly-Leu-Met-NH2 thus seems necessary to elicit changes in P.D. and resistance. (4) As with SP, low doses of physalaemin, eledoisin, kassinin elicited only an increase in PD, the dip appearing with higher concentrations.
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PMID:Effects of tachykinins on the electrical activity of isolated canine tracheal epithelium: an exploratory study. 241 13

Angiotensin I converting enzyme (ACE) and neutral endopeptidase ("enkephalinase"; NEP), were purified to homogeneity from human renal membranes. NEP hydrolyzed substance P (SP) at Gln6-Phe7, Phe7-Phe8, and Gly9-Leu10 and neurotensin (NT) at Pro10-Tyr11 and Tyr11-Ile12. ACE cleaved SP at Phe8-Gly9 and Gly9-Leu10 to release C-terminal tri- and dipeptide (ratio = 4:1). The hydrolysis was dependent on chloride ion and inhibited by captopril. Modification of arginine residues in ACE with cylcohexanedione or butanedione inhibited hydrolysis of SP, bradykinin and Bz-Gly-Phe-Arg (80-93%) indicating an active site arginine is required for hydrolysis of SP. ACE cleaved NT at Tyr11-Ile12 to release Ile12-Leu13. These studies indicate that ACE and NEP, two enzymes which are widely distributed in the body, may be involved in the metabolism of SP and NT.
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PMID:Characterization of the metabolism of substance P and neurotensin by human angiotensin I converting enzyme and "enkephalinase". 241 54

The authors describe the synthesis of Gln-Phe-Phe-Gly-Leu-Met by cyclization of H-Leu-Met-Gln-Phe-Phe-Gly using three different methods. The linear sequence was obtained by a (2+4)-segment condensation. The resulting cyclopeptide showed only a small kinin activity on isolated guinea pig ileum compared to substance P, but it is a full agonist.
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PMID:[Synthesis of cyclic and non-cyclic tachykinin partial sequences. 2. Synthesis of the homocyclic substance P(6-11) hexapeptide]. 241 64

A vector system has been designed for obtaining high yields of polypeptides synthesized in Escherichia coli. Multiple copies of a synthetic gene encoding the neuropeptide substance P (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) have been linked and fused to the lacZ gene. Each copy of the SP gene was flanked by codons for methionine to create sites for cleavage by cyanogen bromide (CNBr). The isolated multimeric SP fusion protein was converted to monomers of SP analog, each containing a carboxyl-terminal homoserine lactone (Hse-lactone) residue (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Hse-lactone), upon treatment with CNBr in formic acid. The Hse-lactone moiety was subjected to chemical modifications to produce an SP Hse amide. This method permits synthesis of peptide amide analogs and other peptide derivatives by combining recombinant DNA techniques and chemical methods.
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PMID:Multiple-copy genes: production and modification of monomeric peptides from large multimeric fusion proteins. 241 4

Two peptides with tachykinin-like ability to contract longitudinal muscle from the guinea pig ileum were isolated from the intestine of the common dogfish, Scyliorhinus caniculus. The amino acid sequence of scyliorhinin I was established as Ala-Lys-Phe-Asp-Lys-Phe-Tyr-Gly-Leu-Met-NH2 and this peptide cross-reacted with antisera directed against the C-terminal region fo substance P. The amino acid sequence of scyliorhinin II was established as Ser-Pro-Ser-Asn-Ser-Lys-Cys-Pro-Asp-Gly-Pro-Asp-Cys-Phe-Val-Gly-Leu-Met- NH2 and this peptide cross-reacted with antisera directed against the C-terminal region of neurokinin A. The mammalian peptides substance P and neurokinin A were absent from the dogfish intestinal tissue.
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PMID:Scyliorhinin I and II: two novel tachykinins from dogfish gut. 242 58

Glycoconjugates with terminal galactose residues were localized in rat spinal cord and spinal ganglia using lectin-HRP conjugates of Griffonia simplicifolia and Glycine max agglutinins. Alternate staining of serial sections with HRP-labelled lectins and an antibody for substance P (SP) showed staining in identical primary sensory neurons with both methods. Similarly, lectin-reactive as well as SP-positive fibers were found in Rexed laminae I and II, Lissauer's tract, the spinal nucleus and tract of the trigeminal nerve, the nucleus commissuralis and a small bundle of fibers just ventral to the central canal. Administration of capsaicin to neonatal rats produced a significant decrease in lectin-reactive fibers of the substantia gelatinosa, and in the number of lectin-reactive sensory neurons. The coexistence of SP with galactose-containing glycoconjugates in spinal ganglion neurons, as well as sensitivity of these cells to capsaicin, provided a basis for classifying the reactive neurons as nociceptive in type. Ligation of dorsal roots resulted in disappearance of lectin reactivity in the spinal cord and caused accumulation of lectin-positive material proximal to the ligature, indicating somatofugal transport of galactose-containing glycoconjugates. Colchicine injection caused an increase in SP reactivity in dorsal ganglion neurons but no change in lectin staining of galactoconjugate. At the ultrastructural level affinity for the lectin conjugates was confined to the Golgi cisternae and the plasmalemma of B-type sensory neurons in the dorsal ganglion. The axolemma of unmyelinated processes stained selectively in dorsal roots and the substantia gelatinosa of the spinal cord. These findings provide evidence for the presence in certain sensory cells of a characteristic galactosylconjugate which may prove to be of significance in nerve function.
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PMID:Evidence for glycoconjugate in nociceptive primary sensory neurons and its origin from the Golgi complex. 242 97

We have investigated certain aspects of the mechanism whereby substance P triggers secretion of 5-hydroxytryptamine (5-HT) from rat peritoneal mast cells in vitro. Substance P-induced release of 5-HT was inhibited following pretreatment of rat peritoneal cells with 0.01-1.0 units/ml neuraminidase; secretion induced by anti-IgE antibody was inhibited by pretreatment with 1.0 units/ml but not by lower concentrations of enzyme. Addition of the sialic acid-rich substances N-acetyl-neuraminlactose (up to 1.0 mM) and mucin (up to 1.0 mg/ml) to substance P in free solution failed to block the activity of the neuropeptide. Limulin, a sialic acid-specific lectin, failed to block substance P-induced secretion of 5-HT, but was found to possess intrinsic non-lytic secretory activity (at 5-20 micrograms/ml). Release of 5-HT induced by limulin was independent of that induced by substance P. A range of octapeptides incorporating the C-terminal sequence Gly-Ser-Phe-Phe, but differing in degree of cationicity and positioning of cationic residues in the four N-terminal positions, were tested for their capacity to antagonise the mast cell-triggering activity of substance P. A peptide incorporating two lysine residues at the N-terminus was found to have partial substance P antagonist activity; no effects on IgE-mediated secretion were observed.
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PMID:The mast cell response to substance P: effects of neuraminidase, limulin, and some novel synthetic peptide antagonists. 242 85


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