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)

Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides.
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PMID:Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A. 1 61

A large-scale purification of monkey brain arylamidase was carried out. Amino acid analyses indicate that the enzyme is rich in acidic amino acids and is poor in cystine. The amino terminal residue was determined to be alanine by dansylation. The enzyme was activated by sulfhydryl compounds. Dithiothreitol was more effective than beta-mercaptoethanol. Bestatin competitively inhibited the enzyme activity and the Ki value was calculated to be 2.5 x 10(-7) M, which was of the same order as that of puromycin. The inhibitions by puromycin and bestatin were reversible. The enzyme hydrolyzed di-, tri-, and oligopeptides including physiologically active peptides. Of physiologically active peptides, enkephalins and Met-Lys-bradykinin, which possess a neutral amino acid at the N-terminal position, were more rapidly hydrolyzed by the enzyme. Peptides such as LH-RH and TRH, which possess a pyrrolidonecarboxylyl group at the N-terminal position, and substance P and bradykinin, which possess a proline residue adjacent to the N-terminal residue, were not hydrolyzed by the enzyme. The Km values for various peptides indicate that the enzyme has higher affinity for oligopeptides than di- and tripeptides. The aminopeptidase activity of the enzyme was also competitively inhibited by puromycin and bestatin. Analyses of the hydrolysis products of various peptides by the dansylation method indicate that the enzyme has both kinin-converting activity and angiotensinase activity.
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PMID:Monkey brain arylamidase. II. Further characterization and studies on mode of hydrolysis of physiologically active peptides. 10 79

Effect of methionine-, leucine-enkephalin (met-, leu-enkephalin) and substance P on the transmission in mouse vas deferens was studied. Both met- and leu-enkephalin inhibited electrically induced contraction of vas deferens at 10(-8)-10(7) M, met-enkephalin being 1.4 times more active than leu-enkephalin. Nalorphine (10(-6) M) antagonized these effects. Substance P (10(-9)-10(-7) M) had no effect on the contraction. Met- and leu-enkephalin (10(-7)-10(-5) M) decreased the high potassium induced [3H]-norepinephrine release from vas deferens, while substance P (10(-6) M) significantly increased it. Nalorphine (10(-5) M) reversed the inhibitory effect of met-enkephalin. These results indicate that these peptides modify the transmission of sympathetic nerve in mouse vas deferens.
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PMID:Effect of enkephalin and substance P on sympathetic nerve transmission in mouse vas deferens. 20 50

The antinociceptive and hypothermic effects of intracisternal administration of 11 endogenous neuropeptides and morphine were evaluated in mice. Of the substances tested, only neurotensin (NT) and beta-endorphin exerted significant antinociceptive and hypothermic effects; NT was the most potent in inducing hypothermia whereas beta-endorphin was the most potent antinociceptive agent via this route of administration. Both NT, and beta-endorphin were, on a molar basis, considerably more potent antinociceptive agents than morphine, [Met]enkephalin, or [Leu]enkephalin. NT-induced analgesia and hypothermia both were significantly dose-dependent. Substance P was found to produce significant hyperalgesia and hyperthermia. Bombesin produced a significant hypothermic effect, whereas somatostatin and luteinizing hormone-releasing hormone (luliberin) produced hyperthermia. None of the other peptides studies [bradykinin, thyrotropin-releasing factor (thyroliberin), melanocyte-stimulating hormone release-inhibiting factor (melanostatin), somatostatin, [Met]enkephalin, and [Leu]enkephalin] produced any significant alterations in colonic temperature or response to a noxious stimulus with the doses tested. These data demonstrate that NT and beta-endorphin, two endogenous brain peptides, are potent in inducing hypothermia and in producing an antinociceptive state.
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PMID:Alterations in nociception and body temperature after intracisternal administration of neurotensin, beta-endorphin, other endogenous peptides, and morphine. 29 52

Bovine substance P has been isolated in pure form from hypothalamic fragments and its complete amino acid sequence determined by studies performed on the intact peptide and on its isolated papain-generated fragments. Direct evidence for the positioning of each residue was obtained, amide assignments were unequivocally established, and the COOH-terminal residue was isolated and identified as Met-NH2. The results of total enzymic digestion performed on each of the peptides obtained argue against the presence of any non-amino acid constituents in the molecule. The amino acid sequence obtained is identical with that previously reported for material isolated form bovine colliculi and from equine small intestine.
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PMID:The amino acid sequence of bovine hypothalamic substance P. Identity to substance P from colliculi and small intestine. 42 29

A new devised arginine derivative, NG-mesitylene-2-sulfonylarginine, Arg(Mts), was employed for the synthesis of hypothalamic substance P and neurotensin. The former was obtained in 74% yield by treatment of the protected undecapeptide amide, Z - Arg(Mts) - Pro - Lys(Z) - Pro - Gln - Gln - Phe - Phe - Gly - Leu - Met(O)-NH2, with methanesulfonic acid in the presence of anisole followed by reduction of the sulfoxide with 2-mercaptoethanol. The latter was obtained in 54% yield by the similar treatment of the protected tridecapeptide ester, Z - Pyr - Leu - Tyr - Glu(OBzl) - Asn - Lys(Z) - Pro - Arg(Mts) - Arg(Mts) - Pro - Tyr - Ile - Leu - OBzl, with methanesulfonic acid. As scavenger, a mixture of anisole-thioanisole-o-cresol (1:1:1, by vol.) was employed to suppress the side reaction, O-mesitylene-2-sulfonation of the Tyr residue.
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PMID:Studies on peptides. LXXXI. Application of a new arginine derivative, NG-mesitylene-2-sulfonylarginine, to the synthesis of substance P and neurotensin. 48 55

X-Pro dipeptidyl-aminopeptidase (EC 3.4.14.1) purified homogeneously from the human submaxillary gland was proved to hydrolyze N-terminal dipeptide Arg1-Pro2 and subsequent dipeptide Lys3-Pro4 from substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-gly-Leu-Met-NH2). Km and V values of hydrolysis of substance P were 2.0 mM and 3.6 mumol/min per mg protein, respectively. In contrast, the N-terminal Arg-Pro of bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) was not cleaved by the enzyme.
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PMID:Successive cleavage of N-terminal Arg1--Pro2 and Lys3-Pro4 from substance P but no release of Arg1-Pro2 from bradykinin, by X-Pro dipeptidyl-aminopeptidase. 68 39

Tissue factor apoprotein and relipidated tissue factor preparations extensively hydrolyze bradykinin, Lys-bradykinin, Met-Lys-bradykinin, substance P, [Asp1, Ile5]-angiotensin II, [Asp1, Ile5]-angiotensin I, and human fibrinopeptide A while acting more slowly on [Sar1, Ile5]-angiotensin II, [Me2Gly1, Ile5]-angiotensin II, bradykinin potentiating pentapeptide from B. jararaca, luteinizing hormone-releasing hormone, melanocyte stimulating hormone-release-inhibiting factor (Pro-Leu-Gly-NH2), and oxytocin. No hydrolysis of thyrotropin-releasing factor or bradykinin potentiating nonapeptide from B. jararaca is observed. Relipidated and apoprotein tissue factor act at identical rates under the conditions of the assay. Dansylation and chromatography of tissue factor-peptide incubation mixtures further indicate that relipidated and apoprotein tissue factor also hydrolyze peptides by identical mechanisms. No fewer than six bonds are hydrolyzed in bradykinin while the angiotensins and substance P are degraded to constituent amino acids. Only the N-terminal alanine is released from fibrinopeptide A. 2-Mercaptoethanol greatly inhibits the hydrolysis of bradykinin by relipidated tissue factor.
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PMID:The hydrolysis of biologically active peptides by bovine lung tissue factor (thromboplastin). 78 91

Secretin, substance P, and vasoactive intestinal peptide (VIP) were studied from the immunological point of view using synthetic hormones and their related peptides which were prepared by the conventional method for peptide synthesis. Immunological properties of these hormones were characterized by radioimmunoassays specific to the respective hormones. Antisecretin antisera (NCC-R-1 and R-801) were generated in rabbits with synthetic porcine secretin absorbed on polyvinylpyrrolidone. Antiserum to substance P (R-400) was produced in a rabbit with synthetic substance P-human alpha-globulin conjugate. Generation of anti-VIP antiserum (R-502) was carried out by immunizing rabbits with synthetic VIP absorbed on polyvinylpyrrolidone. Synthetic polypeptides related to the three hormones that were examined in this study include secretin(4-27), secretin(5-27), secretin(7-27), secretin(11-27), secretin(14-27), secretin(18-27), secretin(1-22)amide, secretin(7-22)amide, Nalpha-tyrosyl-secretin, [1-Tyr]secretin, [4-Ala]secretin, [4-D-Ala]secretin, [4-Ala,5-Val]secretin, [6-Tyr]secretin, substance P(2-11), substance P (3-11), substance P(4-11), substance P(5-11), substance P(6-11), Nalpha-tyrosyl-substance P, [1-Tyr]substance P, [8-Tyr]substance P, [11-Leu]substance P, des-11-Met-substance P, VIP(7-28), VIP(11-28), VIP(18-28), VIP(1-18)amide, and VIP(1-22)AMIDE. The results revealed two antigenic regions at the amino- and carboxylterminal portions of the secretin and VIP molecules. As to substance P, the major antigenic region was located within the 3 to 11 sequence. The proline residue in position 4 and methionine in position 11 seemed to be of special importance. The immunoassays demonstrated the existence of immunoreactivities of these hormones in hot water extracts from various porcine tissues. In the pituitary, VIP and substance P immunoreactivities were detected, whereas secretin was not. Secretin, VIP, and substance P were found in the pancreas, but at low concentrations. Distributions of these hormones in various sites of the gastrointestinal tract were also demonstrated.
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PMID:Immunological aspects of secretin, substance P, and VIP. 83 40

The dose-effect relationships of intraventricularly injected bradykinin, Gly-Arg-Met-Lys-bradykinin (GAML-bradykinin), synthetic substance P and angiotensin II on lever-lifting behavior of rabbits in a variable-interval (VI) 72-second schedule of sweetened water presentation were determined. All peptides used caused dose-dependent decreases in overall rates of VI responding during the experimental session in the following order of potency: angiotensin II greater than bradykinin = substance P greater than GAML-bradykinin. The angiotensin II dose-effect curve was less steep than those of the other peptides. The administration of nearly equimolar doses of the bradykinin potentiating peptides, BPP5a and BPP9a, slightly decreased overall VI response rates and caused a 10- to 20-fold potentiation of the rate-decreasing effect of bradykinin on VI responding. Both angiotensin II and bradykinin caused pauses in responding of dose-dependent duration at the beginning of the experimental session that were followed by normal VI responding. The effect of GAML-bradykinin on VI performance was similar to that of bradykinin and angiotensin II but had a delay of onset of 3 to 6 minutes. In contrast, substance P caused actual decreases in response output and pauses of variable duration interspersed between periods of regular VI responding. At the doses used, both bradykinin-potentiating peptides caused uniform decreases in VI responding throughout the experimental session. Gross behavioral changes caused by the peptides were also observed. After the intraventricular injection of bradykinin or GAML-bradykinin, rabbits showed decreased motility, ptosis, miosis and lowered ears; after angiotensin II, animals remained motionless but with wide open eyes, fully raised ears and no miosis. In turn, substance P caused restlessness and increased locomotion. These results together with reported evidence on other powerful central actions of bradykinin, angiotensin and substance P and on the existence of components of their releasing and destroying enzymatic systems in the brain suggest that linear peptides may play a role in the functioning of the central nervous system.
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PMID:Effect of intracerebroventricular bradykinin and related peptides on rabbit operant behavior. 109 6


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