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)

Specific binding of neurotensin (NT) to mouse peritoneal thioglycollate-elicited macrophages and macrophages differentiated in vitro from bone marrow cells was demonstrated and characterized. NT binding to these phagocytes modulated their phagocytic capacity in a biphasic manner. At concentrations of 10(-14) to 10(-9) M NT, a dose-dependent augmentation of phagocytosis (up to 2-fold) was observed. Further increases in the concentration of NT resulted in a gradual decrease of the augmented response until the basal phagocytic activity (in the absence of NT) was reached. Three partial sequences of NT, NT (8-13), NT (6-13) and NT (1-10), were also effective in augmenting the phagocytic response of thioglycollate elicited macrophages, but the maximal effect was attained at about 10(-7) M and stayed at that level up to a concentration of 10(-5) M. The activity of the three NT partial sequences was comparable to that of substance P and tuftsin. Scatchard analysis of (3H)NT binding to macrophages suggested the existence of two populations of binding sites, a major population of relatively low affinity binding sites and a small population of high affinity binding sites. NT (8-13), NT (6-13), substance P and tuftsin competed with (3H)NT binding to the low affinity sites with a comparable KI to that of NT. NT (1-10) did not compete for the binding at the low affinity sites. It is suggested that NT binding to the high affinity sites leads to enhancement of phagocytosis, whereas its binding to the low affinity sites leads to inhibition of the augmented response. However, the low affinity sites are the sites of interaction of NT (8-13), NT (6-13), substance P and tuftsin with the phagocytes and their saturation with the peptides leads to augmentation of phagocytosis.
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PMID:Enhancement of phagocytosis by neurotensin, a newly found biological activity of the neuropeptide. 618 24

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

Recently, a number of laboratories have postulated the existence of receptor sub-types for substance P. This review is intended to represent a critical appraisal of these reports. In the majority of cases, the evidence for the existence of receptor sub-types has been obtained from observed potency differences of agonists. The problems with this approach are discussed. In addition, information obtained through substance P antagonists, binding studies and investigations of second messenger systems is presented and discussed in relation to the above receptor subdivisions. It is concluded that the present results are consistent with the existence of three receptor sub-types; however, it is suggested that substance P is the natural agonist for only one of these receptors, and that substance K and tuftsin may be the transmitters for the other two receptor sub-types.
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PMID:Are the proposed substance P receptor sub-types, substance P receptors? 620 11

A post-proline cleaving enzyme [prolyl endopeptidase, EC 3.4.21.26] was purified about 3,700-fold from an extract of bovine brain by a series of column chromatographies on DEAE-Sephadex, hydroxyapatite and PCMB-T-Sepharose, and gel filtration on Sephadex G-200 using N-carbobenzoxy-Gly-Pro-beta-naphthylamide (Z-Gly-Pro-2-NNap), thyrotropin releasing hormone (TRH) and oxytocin as substrates. The purified enzyme appeared homogeneous as judged by disc gel and SDS gel electrophoreses. The enzyme was most active at pH 7.5 and 7.2 with Z-Gly-Pro-2-NNap and TRH, respectively, and hydrolyzed peptide bonds involving Pro-X (X=amino acid, peptide, ester and amide) bonds of synthetic substrates, oxytocin, vasopressin, neurotensin, substance P, tuftsin, bradykinin, and insulin B chain. However, the enzyme was inert toward collagen, gelatin, and casein. The enzyme was completely inactivated by diisopropylphosphorofluoridate (DFP), Z-Gly-Pro-chloromethyl ketone and p-chloromercuribenzoate (PCMB), while it was not inhibited by phenylmethane sulfonylfluoride (PMSF) or metal chelators. Determination of the amino acid composition revealed that the enzyme contained 25 half-cystines. Modification of three cysteine residues of the enzyme by PCMB led to complete inactivation. The isoelectric point of the enzyme was 4.8, and the molecular weight was estimated to be 76,000 by ultracentrifugal analysis and 75,000-74,000 by both gel filtration and sodium dodecyl sulfate (SDS) gel electrophoresis, suggesting that the enzyme is present as a monomer. These results indicate that the post-proline cleaving enzyme from bovine brain is very similar to those previously purified from lamb brain and kidney in its enzymatic properties, substrate specificity and physicochemical properties, in sharp contrast with the results obtained by Tate, who reported that the bovine brain prolyl endopeptidase was inert toward oxytocin, vasopressin and bradykinin.
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PMID:Post-proline cleaving enzyme (prolyl endopeptidase) from bovine brain. 636 Oct 10

Rat peritoneal macrophages bind and phagocytoze homologous sialidase-treated erythrocytes at a rate which is dependent on the amount of sialic acid that has been removed from the cells. Increased binding of erythrocytes is observed after the removal of 10-20% of membrane sialic acid, while for phagocytosis at least 30-40% of this substance must be removed. With Vibrio cholerae sialidase only a partial (80%) hydrolysis of rat erythrocyte sialic acid is possible, whereas Arthrobacter ureafaciens sialidase leads to complete desialylation and therefore causes stronger binding and phagocytosis of the erythrocytes than the V. cholerae enzyme. Preincubation of peritoneal macrophages with sialidase impairs binding and phagocytosis. Experiments were performed to account for the stimulation of binding and phagocytosis observed in the presence of native, homologous serum. However, an involvement of immunoglobulins and complement factors of the classical and alternative pathway in the engulfment process has been excluded. Fibronectin, tuftsin and substance P have no influence, either. On the other hand, peanut agglutinin and Erythrina crystagalli agglutinin are potent stimulators of binding and phagocytosis of sialidase-treated erythrocytes, whereas soybean agglutinin has only little and limulin no influence at all. It is concluded that sialidase-treated erythrocytes, having been bound to the beta-galactose-specific lectin on the macrophage surface, are phagocytozed as a function of their number and binding strength to the macrophages. The influence of native serum and especially of the plant lectins on this process is discussed.
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PMID:Binding and phagocytosis of sialidase-treated rat erythrocytes by a mechanism independent of opsonins. 664 29

Proline-containing polypeptides are shown to be sequentially degraded by two aminopeptidases. Clostridial aminopeptidase (EC 3.4.11-) cleaves off any N-terminal amino acid residue including proline from polypeptide chains, but does not cleave the N-terminal secondary peptide bonds involving a prolyl nitrogen. Aminopeptidase P (EC 3.4.11.9) cleaves exclusively such secondary bonds. The two enzymes were immobilized by coupling them covalently to porous amino glass beads. Highly stable preparations were obtained with unchanged pH optimum and thermal stability. The applicability of clostridial aminopeptidase to sequence determination was demonstrated by the time-dependent hydrolysis of enkephalin and Substance P octapeptide. Sequential hydrolysis with the two immobilized enzymes was demonstrated with the proline-containing (Pro-Gly-Pro)10, [Asn1, Val5]angiotensin II, bradykinin, Substance P and tuftsin. Absence of endopeptidase activities was demonstrated by resistance of cytochrome c to hydrolysis and by the ordered release of amino acids during the sequential degradation by immobilized clostridial aminopeptidase and aminopeptidase P.
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PMID:Sequential hydrolysis of proline-containing peptides with immobilized aminopeptidases. 683 Aug 20

A pentapeptide, Ala-Arg-Pro-Ala-Lys, liberated from fibrinogen during plasmin-mediated fibrinolysis, was shown earlier to increase microvascular permeability in rat and human skin. Eighteen new analogues have now been synthesized in addition to the 15 previously prepared and examined for their effect on permeability. The old concept that a tetrapeptide with basic amino acids at both ends and a proline residue adjacent to the N-terminal amino acid is essential for high activity on permeability, has now been challenged. The results obtained with several of the new analogues strengthen this concept. More interestingly, however, the third amino acid, which was found in earlier studies to be less sensitive to exchange, has now been deleted as well as duplicated with only a modest loss of activity of the peptide. The chirality of the C-terminal amino acid, most surprisingly, does not seem to be crucial for peptide activity. Slightly superpotent analogues were obtained on amidation of the C-terminus. In addition, a few naturally occurring peptides, namely tuftsin, substance P, neurotensin and bradykinin, the amino acid sequences of which all exhibit characteristic features of some of our active peptide analogues were investigated in the same test system. Tuftsin displayed a potency equal to that of the pentapeptide. The other three peptides were all highly superpotent in this assay system.
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PMID:Structural requirements for microvascular permeability-increasing ability of peptides. Studies on analogues of a fibrinogen pentapeptide fragment. 684 82

Tuftsin, a natural occurring tetrapeptide, has been found to exhibit several biological activities connected with immune system function. Although little is known about tuftsin's 'biogenesis', much information has been gleaned about its structure-function relationships, which have shown that several features of the molecule are essential for expression of full biological activity. Furthermore, specific receptor sites for tuftsin have been found to exist exclusively on phagocytic cells. Research indicates that tuftsin binding to target cells effect intracellular calcium and cyclic nucleotide levels. Implication of these facts on tuftsin's mode of action are discussed. Basic peptidic segments resembling tuftsin are found in a variety of regulatory peptides. Questions are, therefore, raised as to the biospecificity an cross-reactivity of these sequences. Substance P, one such peptide, which binds with and activates tuftsin receptors, is described. In light of tuftsin's therapeutic potential, assays for its determination have been introduced. When applied to analyze human blood serum of normal as well as of various pathological origins, direct correlation was found between tuftsin levels and susceptibility to bacterial infections.
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PMID:Tuftsin, Thr-Lys-Pro-Arg. Anatomy of an immunologically active peptide. 703 69

The review concentrates on practical applications of computer molecular modeling in peptide drug design. The examples of the predictions (successful or not) made by computational modeling before synthesis of peptide analogs, not the explanations provided after synthesis and biological testing of peptides, are discussed. The review spans over 20 years of predictions made by computer molecular modeling for bradykinin, angiotensin, thyrotropin-releasing factor, tuftsin, substance P, CCK-related peptides, luliberin, alpha-melanotropin and opioid peptides. The described examples are discussed in terms of finding the optimal way to use computer modeling for peptide design. The step-by-step 'technology' of peptide design is outlined in detail.
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PMID:Computational molecular modeling in peptide drug design. 770 73

Aminopeptidase N purified from human placenta actively hydrolyzed various immunomodulating peptides from their N-terminus such as splenopentin, thymopentin, thymic humoral factor gamma 2, tuftsin and rigin in vitro. Aminopeptidase N also actively hydrolyzed neuropeptide hormones (met-enkephalin, somatostatin and neurokinin A) and vasoactive peptides (lysyl-bradykinin and angiotensin III) from their N-terminus. In addition, angiotensin II, secretin, thymopoietin II peptide fragment, motilin, endothelin-I and insulin were tested for hydrolysis by aminopeptidase N. Km and Vmax values for the N-terminal amino acid, Thr, a liberation from tuftsin were 267 microM and 8.33 mumol/min/mg protein, respectively. L-Leucyl-p-nitroanilidase activity in the human placental membrane fraction was almost completely neutralized by anti-aminopeptidase N antibody. Our present study suggests that possible roles for surface enzyme aminopeptidase N in the human placenta would be to down-regulate the action of immunomodulating peptides as well as vasoactive and neuropeptide hormones, and to control both immunology and endocrinology of pregnancy.
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PMID:Possible action of human placental aminopeptidase N in feto-placental unit. 790 13


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