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)

1. In our search for compounds that inhibit the binding of [3H]-substance P (SP) to guinea-pig lung membranes, the dipeptide SP antagonist, FK888, was developed by chemical modification of the parent compound, (D-Pro4, D-Trp7,9,10, Phe11)SP4-11. 2. In a [3H]-SP binding assay using guinea-pig lung membranes and rat brain cortical synaptic membranes, FK888 displaced [3H]-SP binding with a Ki value of 0.69 +/- 0.13 nM and 0.45 +/- 0.17 microM, respectively, in a competitive manner. 3. FK888 inhibited the contraction of guinea-pig isolated ileum induced by SP in the presence of atropine and indomethacin (a NK1 receptor bioassay) with a pA2 value of 9.29 (8.60-9.98). 4. FK888 inhibited contractions of rat vas deferens by NKA (a NK2 receptor bioassay) and of rat portal vein by NKB (a NK3 receptor bioassay) at concentrations at least 10,000 times greater than that required to inhibit contractions of guinea-pig ileum. 5. FK888 also inhibited SP-induced airway oedema in guinea-pig after both intravenous and oral administration. 6. These data demonstrate that FK888 is a potent and selective NK1 antagonist which is active both in vitro and in vivo.
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PMID:Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888. 128 73

To determine whether the N-terminal or C-terminal peptide of substance P (SP) induces granulocyte infiltration in mouse skin, we examined the potencies of SP, the N-terminal peptides SP1-4 and SP1-9, the C-terminal peptides SP4-11 and SP6-11, and a mast cell degranulating agent compound 48/80 in inducing granulocyte (neutrophil and eosinophil) infiltration in the skin of BALB/c mice. The subcutaneous administration of SP (10(-7)-10(-5) M) caused granulocyte infiltration in mouse skin in a concentration-dependent fashion 6 h after the injection. SP1-9 (10(-5)-10(-4) M) also caused granulocyte infiltration in the skin which was associated with mast cell degranulation. However, SP1-4, SP4-11 and SP6-11 (up to 10(-4) M) induced neither granulocyte infiltration nor mast cell degranulation. In addition, compound 48/80 (0.5-50 micrograms/ml) also induced granulocyte infiltration of mouse skin with a concentration-dependent increase in mast cell degranulation. These results indicate that SP induces granulocyte infiltration of mouse skin through mast cell degranulation induced by the N-terminal peptide.
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PMID:[The potencies of substance P, substance P fragments, and compound 48/80 for granulocyte infiltration in mouse skin]. 137 99

A substance P (SP) analog, [D-Pro4,D-Trp7,9,10] SP4-11, is known to inhibit the actions of various structurally unrelated messenger molecules as well as SP. Our studies on the effects of this peptide on the regulation of purified G proteins by receptor showed that at least some of the biological effects of the peptide can be explained by the ability of the peptide to block the activation of G proteins by receptors. Here we report that a novel truncated SP-related peptide, pGlu-Gln-D-Trp-Phe-D-Trp-D-Trp-Met-NH2, inhibited the activation of G(i) or G(o) by M2 muscarinic cholinergic receptor (M2 mAChR) or of Gs by beta-adrenergic receptor in the reconstituted phospholipid vesicles, assayed by receptor-promoted GTP hydrolysis. The inhibition by the peptide was apparently reversible and competitive with respect to receptor binding to G proteins; the inhibition could be overcome by increasing the concentration of receptor in the vesicles and was not altered by changes in the concentration of G protein. The competing effects of the peptide were used to analyze the effect of agonist on receptor-G protein interaction. The concentration change of muscarinic agonist did not alter the inhibitory effects of the peptide on M2 mAChR-promoted GTPase by G(o), which is consistent with the idea that agonist increases the regulatory efficiency of the receptor but does not alter its affinity for G proteins. This new group of compounds (G protein antagonists) is a promising tool to study receptor-G protein interaction quantitatively.
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PMID:G protein antagonists. A novel hydrophobic peptide competes with receptor for G protein binding. 137 92

To determine the mechanism by which substance P (SP) activates human neutrophils, we examined the potencies of SP, the C-terminal peptides SP4-11 and SP6-11, and the N-terminal peptides SP1-9 and SP1-4 for inducing the increase in cytosolic free Ca2+ concentration ([Ca2+]i), superoxide (O2-) generation, and chemotaxis in human blood neutrophils. SP and the C-terminal peptides SP4-11 and SP6-11 and SP6-11 (10(-6)-10(-4) M) induced the increase in ([Ca2+]i, O2- generation, and chemotaxis of the neutrophils dose--dependently, whereas the N-terminal peptides SP1-9 and SP1-4 (up to 10(-4) M) were inactive in inducing these responses. Furthermore, the potencies of the two C-terminal peptides SP4-11 and SP6-11 were not parallel in these three responses. SP6-11 was 7.7-fold more potent in increasing [Ca2+]i than SP4-11, whereas SP4-11 was 16.6-fold more potent in inducing O2-generation than SP6-11. SP6-11 was also 2.1-fold more potent in inducing chemotaxis than SP4-11. Thus, we conclude that the C-terminal peptides of SP induce differential activations of human neutrophils.
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PMID:Differential effects of two C-terminal peptides of substance P on human neutrophils. 170 Dec 27

Substance P (SP) injected into the synovial cavity of the rat knee resulted in an inflammatory response as measured by plasma protein extravasation into the joint capsule. This response was dose dependent over the range of approximately 4 microM to approximately 200 microM. Part of this inflammatory response was mediated via mast cells as pre-treatment of the animals with a mast cell degranulator (compound 48/80) resulted in a 66% reduction of the response. A direct effect of SP on the vascular receptors may also contribute to the inflammatory response as pre-treatment with the substance P antagonist (SPA) D-Pro4 D-Trp7,9,10 SP4-11 also reduces the inflammatory response. Intra-articular injections of the H1 blocker diphenhydramine or the H2 blocker cimetidine significantly blocked the SP-induced inflammatory response. The 5-hydroxytryptamine (5-HT) antagonist methysergide proved to be even more potent in blocking the SP-induced inflammatory response. No synergistic inhibition was observed with combinations of the different antagonists. Intra-articular injections of 5-HT elicited a much more pronounced inflammatory response than that produced by a 10-fold higher concentration of histamine. The results suggest that SP produces increased vascular permeability partly via direct actions on the blood vessels and partly via mast cells. The inflammatory response occurring via mast cells appears to be mediated by histamine and to a greater extent by 5-HT.
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PMID:Mediators of substance P-induced inflammation in the rat knee joint. 170 85

1. Experiments were performed in cats anaesthetized with pentobarbitone. Laser Doppler flowmetry was used to assess the responses of knee joint blood vessels to nerve stimulation under control conditions and in the presence of different adrenoceptor antagonists in order to establish the nature of neurotransmitters released from articular nerve fibres. 2. The posterior articular nerve (PAN) supplying the knee was stimulated at different intensities, and frequency-response curves were obtained. In fourteen animals electrical stimulation of PAN produced an initial vasoconstriction during stimulation which in eight of these was followed by a prolonged dilatation on cessation of stimulation. The constrictor response was increased as a function of frequency but was little altered with increasing intensity beyond a threshold level. 3. The constrictor response to electrical stimulation of PAN was markedly reduced by the alpha-adrenergic antagonist phentolamine (10(-5) M, the alpha 1-blocker prazosin (10(-5) M), and guanethidine (10(-5) M) which inhibits the release of noradrenaline, ATP, and neuropeptide Y from sympathetic nerve endings. 4. The constrictor response to PAN stimulation was unaffected by the alpha 2-blocker rauwolscine and the P2-purinoceptor desensitizer alpha,beta-methylene ATP. 5. The dilator response was due to activation of afferent fibres as it could also be produced by direct electrical stimulation of the L7 dorsal roots. 6. The dilator response to stimulation of PAN or the L7 dorsal root was reduced by prior intra-articular injection of 100 micrograms of the substance P antagonist D-Pro4-D-Trp7,9,10-SP4-11. 7. These results suggest that the vasoconstrictor response to electrical stimulation of PAN is most likely to be mediated via noradrenaline acting mainly upon alpha 1-adrenoceptors. As the dilator response to articular nerve stimulation is reduced by a substance P antagonist, the mediator inducing this response may be substance P or a related neurokinin.
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PMID:Alterations in cat knee joint blood flow induced by electrical stimulation of articular afferents and efferents. 170 71

This study was an investigation of the effects of the tachykinin antagonists, spantide and (D-Pro4, D-Trp7,9,10)substance P 4-11, injected intracerebroventricularly (ICV), on the locomotor and behavioural responses of guinea-pigs to substance P (SP) injected ICV and to naloxone-induced morphine withdrawal. SP, 50 nmol, produced increased locomotor activity and behaviour that mimicked the response induced by injection of naloxone hydrochloride, 15 mg/kg, in guinea-pigs treated 2 h previously with morphine sulphate, 15 mg/kg. Spantide or (D-Pro4, D-Trp7,9,10)SP4-11, 10 nmol, reduced the locomotor and behavioural responses to SP and to morphine withdrawal. The results support the suggestion that SP or a related tachykinin might be a mediator of the opioid withdrawal response in the central nervous system as has been proposed for the enteric nervous system.
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PMID:Tachykinin antagonists inhibit the morphine withdrawal response in guinea-pigs. 171 41

Calcitonin gene-related peptide (CGRP) produced a dose-related wheal and flare reaction in human skin at doses of 12.5 to 50 pmol. The flare response but not the wheal response to CGRP and substance P were inhibited by prior treatment of the subject with oral chlorpheniramine, 16 mg. CGRP, but not substance P, was potent in producing a delayed erythema and surrounding pallor in human skin, which peaked at 1 h and persisted for more than 3 h after injection, when wheal and flare responses had subsided. The delayed response was accompanied by infiltration of polymorphonuclear leukocytes. The delayed erythema and pallor produced in response to CGRP were not inhibited by oral chlorpheniramine, or by 4% prilocaine injected locally. CGRP released histamine from rat peritoneal mast cells over the concentration range 2.5-10 microM. CGRP was about fourfold less potent than substance P in releasing histamine. The substance P analogue, [D-Pro4, D-Trp7,9,10]SP4-11 10 microM, and benzalkonium chloride 10 microM inhibited histamine release from rat mast cells stimulated by either CGRP or substance P.
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PMID:Some effects of calcitonin gene-related peptide in human skin and on histamine release. 241 14

Substance P (SP), somatostatin (Som), and vasoactive intestinal polypeptide (VIP) induced a concentration-dependent release of histamine from isolated rat peritoneal mast cells. The release of histamine induced by these neuropeptides was inhibited by preincubation of the cells with the SP analogue [D-Pro4,D-Trp7,9,10]-SP4-11 (SP-A) (10 microM), and also by benzalkonium chloride (10 microM). In addition, SP-A inhibited histamine release induced by compound 48/80, whilst that induced by goat anti-(rat-IgE) was unaffected. In human skin, intradermal injection of SP, Som, or VIP produced flare and wheal responses. The flares to all three peptides were inhibited by preinjection of the skin with SP-A (25 pmol), whilst the wheal responses were unaffected. It is concluded that the receptors mediating histamine release and the flare response are similar, and that SP, Som, and VIP are acting at a similar receptor to produce these effects. It is probable that this receptor is also the site of action of compound 48/80.
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PMID:On the actions of substance P, somatostatin, and vasoactive intestinal polypeptide on rat peritoneal mast cells and in human skin. 241 71

A dose-response relationship for substance P and contraction of the lung parenchyma strip of the guinea-pig could only be obtained in the presence of a mixture of bacitracin, 1,4 dithio-L-threitol and ethylenediamine tetracetic acid, all at 100 microM, or in the presence of captopril, 1.8 mM. Substance P (50 nM) caused no contraction by itself but produced a shift to the left of the dose-response curve for histamine with a mean dose-ratio of 1.4 +/- 0.2 (S.E. of mean). The peptides physalaemin, eledoisin and kassinin were all approximately equipotent with substance P on the lung strip, in the presence of peptides inhibitors. [D-Pro4, D-Trp7,9,10]-SP4-11, produced dose-related inhibition of the contraction induced by substance P. Substance P activity in guinea-pig lung declined exponentially with a half-time of 2.3 min: bacitracin, dithiothreitol and EDTA (all 100 microM) increased this to 7.2 min and captopril (1.8 mM) to 5.1 min.
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PMID:Contraction of guinea-pig lung parenchymal strips by substance P and related peptides. 242 Feb 97


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