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)

We have synthesized a series of 12 analogs of the undecapeptide substance P in order to perform a structure-activity study of this peptide. In the present work, each residue was substituted by L-alanine, and the C-terminal amide was replaced by the free carboxyl in order to pinpoint biologically important side chains and functional groups. The synthesis of the analogs was carried out by the automatic solid-phase method. Couplings were performed by the symmetrical anhydride procedure. After cleavage with liquid HF, the peptides were purified by gel filtration and ion-exchange chromatography. Their purity was assessed by thin-layer chromatography, paper electrophoresis, amino acid and elemental analyses, and high pressure liquid chromatography. They were tested for biological activity in vitro on the ileum of the guinea pig, the mesenteric vein of the rabbit, and the vas deferens of the rat, and in vivo by measuring their effect on the blood pressure of the rat.
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PMID:Synthesis of peptides by the solid-phase method. V. Substance P and analogs. 615 84

The miotic potency of eleven naturally occurring polypeptides and poly-DL-alanine was tested on the isolated anterior segment of hooded rat and golden hamster eyes in order to gain information on the chemical nature of the peptides or classes of peptides which may be regarded as possible mediators of the miotic response of the mammalian eye to chemical irritants or mechanical or surgical trauma. Substance P, P-octapeptide, physalaemin and eledoisin, and eledoisin related peptide were found to be potent miotics on these preparations, yielding ED50 values in the range of 8 to 95 nM and complete pupillary constriction in the range of 100 to 1000 nM. This is comparable to the miotic potency of carbachol or serotonin. All of these peptides share a C-terminal sequence Phe-X-Gly-Leu-Met-NH2 (where "X" is a variable amino acid) which is characteristic of all tachykinins. Six other biologically active peptides or the synthetic poly-DL-alanine had no measureable miotic effect on these preparations up to a final concentration of 1000 to 10,000 nM. The miotic effect of SP on the rat iris was effectively, but not completely antagonized by the presence of 10(-7)M atropine sulfate in the incubation medium. Preliminary results indicate that the miotic effect of physalaemin, eledoisin and eledoisin related peptide on the anterior segment of rat eyes is similarly antagonized by atropine.
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PMID:The mechanism of peptidergic miosis. I. The structural basis of miotic potency among biologically active polypeptides. 617 53

Substance P (SP) and somatostatin (SRIF) are known to inhibit the nicotine-induced release of catecholamines (CAs) from isolated adrenal chromaffin cells in culture22,24. In order to characterize the receptors mediating this action, we have tested several SP and SRIF analogues for their effects on release of [3H]L-norepinephrine ([3H]NE) from chromaffin cell cultures. SP-free acid and a series of 11 SP analogues, in which each amino acid of SP is replaced in turn by L-alanine, all inhibited the nicotine-induced release of [3H]NE from these cultures. The rank order of potency of the analogues for this action was similar to their reported order of potency in other SP-responsive tissues. The least potent were SP-free acid, [Ala7]-SP, [Ala10]-SP, [Ala8]-SP and [Ala11]-SP, while the potencies of the Ala 1 to 6 analogues and [Ala9]-SP were closer to that of SP. [Leu7]- and [Leu7,8]-SP had potencies similar to that of SP. SP itself had no effect on basal [3H]NE release and only the highest concentrations of some of the analogues tested had an effect (enhancement) on basal [3H]NE release. The results suggest that adrenal chromaffin cells possess a specific SP receptor mediating inhibition of agonist-induced CA release and that the binding site of this receptor shares similar structural requirements with the binding site of the SP receptor on other tissues. Several SRIF analogues, which have been previously shown to be more potent than native SRIF at selective SRIF receptors2,3,31, 35, were compared to SRIF for effects on [3H]NE release from chromaffin cell cultures. These analogues were found to be active but less potent than SRIF in inhibiting nicotine-induced [3H]NE release from these cultures, suggesting that the site mediating this action differs in its structural requirements from the SRIF receptor found in some other tissues.
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PMID:Characterization of substance P and somatostatin receptors on adrenal chromaffin cells using structural analogues. 618 47

Angiotensin-converting enzyme was solubilized with papain from a particulate fraction of rat brain and purified to apparent homogeneity by a procedure including DEAE-cellulose, hydroxylapatite, Sephadex G-200, Cys(Bzl)-Pro-Sepharose, and ricin-Sepharose chromatography. Bradykinin potentiators, SQ 14,225, and Arg-Pro-Pro strongly inhibited the activity of the purified enzyme, whereas Phe-Ala, phosphoramidon, and pentobarbital exerted little inhibitory effect on the activity. Among neuropeptides investigated, substance P, bradykinin, and Leu-enkephalin (Arg6) exerted strong inhibitory actions on the enzyme. Furthermore, the latter two peptides were shown to be good substrates for the enzyme. Thus, angiotensin-converting enzyme of rat brain is distinct from endogenous enkephalinase and may interact with various neuropeptides located in the brain.
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PMID:Purification and inhibition by neuropeptides of angiotensin-converting enzyme from rat brain. 619 11

Immunoreactive dynorphin (ir-Dyn), immunoreactive leucine-enkephalin (ir-Leu-Enk) and various other neuropeptides were measured in acid extracts of bovine adrenal medulla and isolated adrenal chromaffin cells. Their respective levels ranged as follows: Leu-Enk greater than Dyn greater than bombesin greater than vasoactive intestinal peptide (VIP) greater than neurotensin greater than substance P. Comparisons of the total catecholamine levels with the levels of Leu-Enk in both extracts gave ratios in the same order of magnitude (2600, tissue extract and 5000, cell extract). However, the catecholamine/Dyn ratio in the tissue extract (138 000) was much higher than that found in the cell extract (20 180), suggesting a possible selective degradation of Dyn in tissue extract as compared with cell extract or an induction of Dyn biosynthesis in cells which have been isolated from their natural microenvironment. Immunofluorescence staining of isolated chromaffin cell sections revealed the presence of ir-Dyn in 5 to 10% of the total cell population. To localize ir-Dyn in regard to Leu-Enk and catecholamines, adrenal chromaffin cells were separated into three populations (I, II, and III) on a stepwise bovine serum albumin (BSA) gradient. Relative high levels of ir-Dyn were measured in cell layer I (4 pmol/10(6) cells), a cell population enriched in noradrenaline. However, ir-Leu-Enk was more concentrated in cell layers II and III (5.3 and 8.3 pmol/10(6) cells), two populations enriched in adrenaline. Isolation and high pressure liquid chromatography (HPLC) analysis of adrenomedullary Dyn indicated the presence of at least five molecular forms corresponding to Dyn-(1-11), Dyn-(1-12), Dyn-(1-13), Ala-containing-Dyn-(1-13) and a nonidentified molecule eluting closely to Dyn-(1-13). These data indicate that adrenal ir-Dyn and ir-Leu-Enk have distinct cellular distributions. In addition, the identification of Dyn fragments in bovine adrenal medulla indicates that these short peptides may be considered as natural active forms of Dyn.
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PMID:Dynorphin and enkephalins in adrenal paraneurones. Opiates in the adrenal medulla. 620 34

Two low molecular weight fibrin(ogen) degradation products, 6A (Ala-Arg-Pro-Ala-Lys) and 6D (Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys) that are known to increase vascular permeability were injected together with bradykinin, substance P, neurotensin, histamine or tuftsin into the dorsal skin of rats. Effects on microvascular permeability were evaluated as leakage of intravenously injected 125I-labelled human serum albumin to tissues. It was found that peptide 6A potentiated the leakage caused by bradykinin and also, to a minor extent, that caused by substance P over a 30 min period, but not of any other substance. Peptide 6D increased bradykinin-induced leakage to a lower degree than did peptide 6A. Thus, it is shown that products resulting from fibrinolysis exert a selective effect upon the action of bradykinin and of substance P.
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PMID:Enhancement of the permeability-increasing effect of bradykinin and substance P by a peptide derived from fibrinogen. 620 7

Two fibrin-derived peptides. Ala-Arg-Pro-Ala-Lys and Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys, increase microvascular permeability in rat skin. In the present investigation it is shown that they release histamine from rat mast cells and that their effect on microvascular permeability can be inhibited by previous histamine depletion of the skin or treatment with an antihistamine, the H1-blocker mepyramine maleate. It is concluded that histamine release contributes to the permeability-increasing effect of these peptides as well as of the structurally similar peptides bradykinin, substance P and neurotensin.
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PMID:Fibrin-derived vasoactive peptides release histamine. 620 10

1. A thiol proteinase from human pituitaries was purified approximately 400 fold and shown to have different chromatographic properties from that of calf brain. Among substrates cleaved were myelin basic protein, histones, beta-lipotropin, neurophysin, and Substance P. 2. The enzyme showed properties associated with a cathepsin-B like enzyme: dependence on -SH groups, pH optimum of 6.5, inhibition by leupeptin and a synthetic analog, Boc-D-Phe-Pro-arginal, and cleavage of dipeptidyl arylamides with basic residues adjacent to or penultimate to the chromatographic grouping. 3. Membranes present in the P2 fraction of rat brain contained three or more enkephalinases when submitted to DEAE-cellulose chromatography. Further purification on an IgG-Sepharose affinity column prepared with antibody to lung angiotensin converting enzyme indicated the presence of dipeptidyl carboxypeptidase(s) with properties distinct from those of ACE. In addition, the DEAE-cellulose fractions contained various aminopeptidase activities when tested with Leu-Gly-Gly, Leu-Nap, and Ala-Ala-Nap as substrates.
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PMID:Peptide processing in the central nervous system. 625 8

Proline-containing dipeptidyl-4-nitroanilides have been synthesised and subjected to dipeptidyl peptidase IV-catalysed hydrolysis at high enzyme concentrations to collect information on the conformational specificity of the enzyme active site for a nonscissile bond. Descriptions of the biphasic kinetics were carried out in terms of cis/trans interconversion of the substrates. The results show that the enzyme can cleave only the trans-conformation of the substrate. The competitive inhibition by Gly-Pro-OH and Ala-Pro-OH is also specific for the trans form of the dipeptides. The interpretation of the results obtained from these kinetic studies has led to proposals for the stepwise cleavage of biologically active peptides like substance P and beta-casomorphine by dipeptidyl peptidase IV.
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PMID:The conformation around the peptide bond between the P1- and P2-positions is important for catalytic activity of some proline-specific proteases. 634 Jul 41

Human placenta is surprisingly rich in post-proline dipeptidyl peptidase activity. Among various cell fractions, microsomes have the highest specific activity. A homogeneous enzyme preparation is obtained in a six-step purification procedure. The final preparation appears homogeneous upon dodecyl sulfate electrophoresis, but analytical isoelectric focussing reveals various active bands with isoelectric points in the range of pH 3-4. The enzyme is a glycoprotein containing about 30% carbohydrate. Treatment with neuraminidase lowers the isoelectric points but does not reduce the heterogeneity of the band pattern. The subunit molecular weight is 120000 as estimated by dodecyl sulfate electrophoresis, whereas Mr of the native enzyme is greater than 200000, as can be concluded from gel filtration experiments. The purified dipeptidyl peptidase cleaves various synthetic and natural peptides, including substance P, kentsin, casomorphin and a synthetic renin inhibitor. In general, the specificity of the placenta peptidase is similar to that of post-proline dipeptidyl peptidase from other sources. Phenylalanylprolyl-beta-naphthylamide (Km = 0.02 mM, V = 92 U/mg) is the best substrate among various synthetic peptide derivatives. Only peptides with a free N-terminal amino group and proline, hydroxyproline, or alanine in position 2 of the N-terminal sequence are cleaved. However, X-Pro-Pro-. . . structures, e.g. as in bradykinin, are not attacked. 1 mM bis-(4-nitrophenyl)phosphate or 1 mM diisopropylfluorophosphate completely inactivate the peptidase within 30 min at 30 degrees C (pH 8). The peptidase is also completely inhibited by 1 mM Zn2+ and by other heavy metals.
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PMID:Isolation and characterization of dipeptidyl peptidase IV from human placenta. 675 24


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