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

The action of an eledoisin-hexapeptide analogue (EH) upon learning and memorising processes of 48 male Wistar laboratory rats aged between 5 and 6 months was studied and is reported in this paper. The animals suffered from neurogenic hypertension which had been experimentally induced by applying emotional stress. A comparison between the action of EH (Lys-Phe-Ile-Gly-Leu-MetNH2) and that of Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2) on conditioned-reflex learning in the intact rat had been reported by the authors in one of their previous papers [7]. The following results were obtained with regard to EH and its action upon rats with neurogenic hypertension. The learning process was favoured, as it had been by 2 or 3 weeks of exercise. Defective learning and memorizing process as well as impaired behavioural patterns, interpreted as neurotic phenomena, were normalized by doses of 250 microgram/kg and 500 microgram/kg. Blood pressures were reduced, depending on dosage. The action of the EH analogue used on the central nervous system was stronger than that on blood pressure. Discontinuance of peptide application was followed by the phenomenon of "state-dependent learning". The results are likely to suggest possible involvement of such peptide sequences in the regulation of processes which are relevant to the whole. That effect is of particular interest, as Substance P is under discussion as a transmitter or modulator in mammals.
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PMID:Action of substance P on neurotico-hypertensive rats. 9 44

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

The actions of both Substance P, a potential neurotransmitter or modulator and of a shortened analogue on learning and memorizing processes are reported in this paper. Sixty male rats, aged 22, 14, and 10 weeks, were exposed to Substance P (Arg-Pro-Gln-Gln-Phe-Gly-Leu-MetNH2) and to a shortened hexapeptide analogue (Lys-Phe-Ile-Gly-Leu-MetNH2), doses being 250 microgram/kg and 500 microgram/kg, to test their action upon learning and memorizing processes, such as acquisition, retention, and ecphoration, by means of a conditioned-reflex locomotor defense method. Response time of all three age groups as well their retention and ecphoration were normal under the impact of hexapeptide. The effects of Substance P were decline of retention in juvenile animals (10 weeks of age) and coupling between the processes of central-nervous afference synthesis, on the one hand, and the efference integral related to motoricity, on the other, in both juvenile and adult animals. A retention test was conducted and showed that discontinuation of application of either peptide over 4 d was followed by complete inhibition of ecphoration. Learning and memorising processes were restorable by reapplication of the peptides. These findings were defined as "state-dependent learning". Only slight variation under the impact of both Substance P and the analogue was recordable by non-invasive measurement of systolic blood pressure.
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PMID:Conditioned-reflex learning of normal juvenile and adult rats exposed to action of substance P and of an SP analogue. 50 32

The synthesis and biological evaluation on thermoregulation of 39 peptides related to bombesin (structural analogues or other naturally occurring peptides) are described. The bioassay system reported measures the ability of peptides injected intracisternally to lower body temperature of cold (4 degrees C) exposed rats. The most potent analogues of bombesin were those in which positions one to five (not included) were altered, indicating that the decapeptide C terminal was sufficient for full potency. Gln at the seventh position and Gly at the 11th position could be replaced by D-Gln and D-Ala (but not D-Pro or D-Phe), respectively, without any change in potency. Methionine at the 14 position could be replaced with its D isomer with retention of 10% biological activity. Any other alteration of the C terminus (deletions or free acid with the exception of the N-methylamide) drastically reduced the biological potency of those peptides. Among other naturally occurring peptides, alytesin was found to have 100% of bombesin potency whereas litorin, neurotensin, xenopsin, substance P, physalaemin, and eledoisin were found to be in the order of 10(4) times less potent. The shortest peptide found to have full biological activity is the octapeptide des-Glp-Gln-Arg-Leu-Gly-Asn[D-Glp7, D-Ala11]-bombesin.
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PMID:Bombesin, bombesin analogues, and related peptides: effects on thermoregulation. 65 96

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

[Tyr8]-substance P, an undecapeptide having the structure Arg-Pro-Lys-Pro-Gln-Gln-Phe-Tyr-Gly-Leu-Met-NH2, has been synthesized by the solid-phase technique on a Beckman automatic peptide synthesizer, appropriately purified and biologically characterized. At twice the dosage, [Tyr8]-substance P showed the same biological activity response as synthetic substance P for stimulation of contraction of the isolated guinea pig ileum and for decrease in the systemic blood pressure of dogs. On the dog's blood pressure, no qualitative differences were observed, but on the isolated gut, the Tyr8 analog gave a more gradual increase in the muscle tone than synthetic substance P. [Tyr8]-substance P released, in vitro, the luteinizing and follicle-stimulating hormones at a very high dosage but did not release growth hormone, prolactin, or thyrotropin.
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PMID:Synthesis and some biological activities of the tyrosine-8 analog of substance P. 124 14

A human urine serine proteinase chymotrypsin like hydrolyzes the peptide bonds: Phe-Ser (kinin); Gly-Gly, Leu-Arg, Phe-Lys (neuropeptides) and Gln-Gln (substance P). Endopeptidase H2 hydrolyzes better oligopeptides with 4 to 18 aminoacid residues than larger peptides, it does not hydrolyzes kininogen or proenkephalin. The enzyme behaves as an oligoendopeptidase.
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PMID:Further characterization of endopeptidase H2 a serine proteinase from human urine. 128 11

1. We have evaluated the ability of substance P (SP), neurokinin A (NKA) and the selective NK2 receptor agonist [beta-Ala8]-NKA(4-10) to induce superoxide anion (O2-) production and prostanoid (prostaglandin E2, thromboxane B2) release from alveolar macrophages (AMs) isolated from control or actively sensitized guinea-pigs. 2. The dose-response curves for NKA and SP were shifted to the left (three orders and one order of magnitude, respectively) in AMs isolated from sensitized animals, with no variation in maximal effects. 3. By evaluating the effects of [beta-Ala8]-NKA(4-10), we observed that not only was the concentration-response curve shifted to the left in both the functional parameters examined, but also maximal effects were significantly enhanced in AMs isolated from sensitized guinea-pigs. 4. This varied responsiveness seems to be specific for tachykinins, as it was not reproduced by another AM stimulant, the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). 5. Only small amounts of beta-glucuronidase were released following tachykinin or ovalbumin stimulation both in control and sensitized AMs. 6. These results indicate that AMs isolated from sensitized guinea-pigs show an increased responsiveness to NK2 receptor stimulation and further stress the role played by AMs in allergic lung diseases.
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PMID:Enhanced responsiveness of ovalbumin-sensitized guinea-pig alveolar macrophages to tachykinins. 128 23

A capsaicin test involving peripheral nociception, which produces behaviour similar to that elicited by formalin, is described in mice. Capsaicin was injected subcutaneously (s.c.) into the dorsal surface of a hindpaw and the time the animals spent licking the paw was recorded. Doses of capsaicin of 6.25-1600 ng induced nociception, during a period of 5 min, starting immediately after injection and disappearing completely at 10 min. Intrathecally (i.t.) administered [D-Arg1,D-Trp7,9,Leu11]substance P (spantide), a tachykinin antagonist and [D-Phe7,D-His9]substance P (6-11), a selective antagonist of substance P (SP), inhibited the capsaicin-induced behaviour, in a dose-dependent manner. This licking behaviour was also inhibited by intrathecal administration of SP antiserum but not by somatostatin (SOM) antiserum. Intrathecal pretreatment with capsaicin resulted in a marked reduction of the licking response, following subcutaneous injection of capsaicin into the paw. Capsaicin-induced licking was not affected by intrathecal administration of cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-(OBz)-Thr], a SOM antagonist and by intrathecal pretreatment with cysteamine, a SOM depletor. This nociceptive test may allow discrimination between SP- and SOM-mediated responses in the spinal cord of the mouse.
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PMID:The capsaicin test in mice for evaluating tachykinin antagonists in the spinal cord. 128 12


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