UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The assumption that life changes and stressful events can alter host defense is based mainly on studies of changes in a variety of immune and inflammatory reactions. Whether those changes also confer an increased susceptibility to infectious agents and neoplasms, or modify the course of such diseases, is still less well substantiated. Nonetheless, psychological and neural modulation of immunity has recently been possible to approach from a mechanistic viewpoint. For instance, generation of a variety of lipid mediators from arachidonic acid may be under control of dietary and endocrine factors that can be affected by stress. Since these lipids, eg, lipoxygenase products, are potent regulators of leukocyte functional responses, their significance as one of several mechanisms is discussed. The role of various neuropeptides in leukocyte function has only recently been discovered. Since the release of, eg, substance P, enkephalins, and endorphins, which all have modulating effects on leukocyte functional responses, is under neural control and can occur in the vicinity of immunocompetent cells, they might constitute one of several links between the mind and the immune system.
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PMID:Stress-related modulation of immunity: a review of human studies. 331 52

Formylmethionylleucylphenylalanine (FMLP) is a synthetic analogue of bacterial chemotactic factors. We studied the contraction of human airway tissue in vitro by FMLP. FMLP induced a concentration-dependent contraction of all bronchial spiral strips studied (n = 45). The maximum tension generated in response to FMLP was 86.6 +/- 7.0% (SE) of the maximum response to histamine. The contraction was not reduced by the histamine H1-receptor antagonist pyrilamine, the cyclooxygenase and lipoxygenase inhibitors indomethacin and BW755C, the muscarinic antagonist atropine, or capsaicin which depletes stores of substance P. The concentration-response curve was shifted to the right by the polypeptide antagonist N-t-BOC-phenylalanylleucylphenylalanylleucylphenylalanine and the leukotriene antagonist FPL 55712. When 2 successive FMLP concentration-response curves were performed the maximum response was significantly reduced from 114.8 +/- 9.1% of the histamine maximum to 39.3 +/- 6.1%. The contraction of human airways in vitro by an agent that is structurally and functionally similar to chemotactic peptides released from bacteria may have important implications in airway disease.
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PMID:Formyl peptide-induced contraction of human airways in vitro. 394 25

The contractile response of guinea-pig tracheal preparations with or without epithelium to substance P has been studied in the presence or absence of thiorphan, an endopeptidase 24.11 inhibitor, paying special attention to the kinetics of the response. Without thiorphan, the response to substance P was greater in tracheal preparations without epithelium than in tracheal preparations with epithelium. The concentration-response curve was shifted to the left in the absence of the epithelium. In the presence of 10 microM thiorphan, the maximal contractile response induced by single doses of substance P (0.1 to 10 microM) was lower in tracheal preparations without epithelium. The maximal responses required 10 min in tracheal preparations with epithelium and 2 min in tracheal preparations without epithelium. These epithelium-dependent differences of reactivity remained in the presence of lipoxygenase or cyclooxygenase inhibitors and of selective antagonists of muscarinic, serotoninergic and histaminergic receptors, after the pre-treatment of tissues with capsaicin or compound 48/80 and in the presence of tetrodotoxin. The profile of the cumulative concentration-response curves for substance P was largely dependent on the time between two successive doses. When this time was short (2-4 min), curves established with or without the epithelium were parallel and both reached similar maximal values (2696 +/- 214 mg and 2780 +/- 62 mg, respectively). The curve in tracheal preparations without epithelium was slightly shifted to the left (EC50s: 24 +/- 10 nM and 78 +/- 19 nM). When this time was longer (10 min, ie corresponding to the time required for a full response to a single dose in intact trachea) the potency of substance P was not modified (EC50s: 13 +/- 3 nM and 52 +/- 11 nM), but a lower maximal response was observed with tracheal preparations without epithelium (1440 +/- 182 mg and 2832 +/- 209 mg). Similar results were observed with neurokinin A and neurokinin B. Thus, the removal of the epithelium led to a more rapid contraction and to a decrease of the maximal response to neurokinins, ie a decreased intrinsic activity, a property known to be drug- and tissue-dependent. These data suggest that the intrinsic activity of drugs depends on the cellular environment of the target cells in a tissue and is partly related to the diffusion and metabolism of drugs and to drug-induced hyporeactivity of the target cells.
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PMID:Epithelium modulates the kinetics of the response to substance P and its intrinsic activity in the guinea-pig trachea. 752 61

Somatostatin enhances an inward rectifier K conductance in cultured locus coeruleus neurons, while substance P reduces an inward rectifier K conductance in cultured nucleus basalis and locus coeruleus neurons. The role of arachidonic acid metabolites in these responses was studied. The somatostatin-induced response was reduced by phospholipase A2 inhibitors, non-specific lipoxygenase inhibitors and specific 5-lipoxygenase inhibitors. A cyclooxygenase inhibitor and a 12-lipoxygenase inhibitor had no effect. 5(S)-HPETE occasionally increased the K conductance, but failed to occlude the somatostatin response. The substance P response was suppressed by a 5-lipoxygenase inhibitor but not by a 12-lipoxygenase inhibitor. These results suggest that the 5-lipoxygenase pathway is not a specific messenger of either one of these responses, but that it plays a more general role in maintaining or enhancing the effectiveness of both somatostatin and substance P responses.
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PMID:The role of arachidonic acid metabolism in somatostatin and substance P effects on inward rectifier K conductance in rat brain neurons. 753 42

In order to investigate the functional role of endothelium and vasoeffector mechanism in cerebrovascular responses to neuropeptides, the stainless steel cannula inserting method was applied to examine the responses to intraluminally-applied bradykinin, substance P and vasopressin in isolated and perfused canine basilar arteries. In control vessels with intact endothelium, each neuropeptide induced a monophasic dilation at lower doses, and a biphasic response, i.e., an initial dilation followed by a secondary constriction, at higher doses. The dilation was significantly reduced and the constriction was significantly enhanced, while the dilation to papaverine was not modified by endothelial removal with intraluminal saponin. The same tendency was observed in the responses after extraluminal treatment with oxyhaemoglobin. The monophasic constrictions to prostaglandin F2 alpha and potassium chloride were significantly potentiated by the endothelial removal. The augmented constrictions to the neuropeptides were significantly diminished by indomethacin (a cyclooxygenase inhibitor), OKY-046 (a thromboxane synthetase inhibitor) and nimodipine (a dihydropyridine calcium antagonist), but not by AA-861 (a lipoxygenase inhibitor). These results suggest that the neuropeptide causes an endothelium-dependent dilation and a constriction of smooth muscles, and that the enhanced constriction might be relevant in part with thromboxane A2, linked with calcium influx into smooth muscle cells in cerebral arteries.
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PMID:Vasoconstrictor mechanism of neuropeptides augmented after endothelial removal in isolated, perfused canine basilar arteries. 754 80

The i.v. administration of substance P (SP, 0.25-16 micrograms/kg) or of the selective metabolic stable NK-1 agonist, [Glp6,Pro9]SP-(6-11) (septide, 0.03-0.25 microgram) to atropine-treated guinea pigs or to isolated perfused lungs triggered a dose-dependent bronchoconstriction, which was enhanced in animals actively sensitized to ovalbumin. In vivo, bronchial hyper-responsiveness was restricted to SP and to septide, inasmuch as neurokinin A (0.06-1 microgram/kg)- or capsaicin (0.5-32 micrograms/kg)-induced bronchoconstriction were not modified. In contrast, isolated lungs from sensitized guinea pigs exhibited an increased bronchoconstriction also in response to capsaicin (0.01-10 micrograms), which was inhibited by atropine in the medium. Pretreatment of actively sensitized guinea pigs either with indomethacin plus mepyramine, the lipoxygenase inhibitor BW A4C or with the platelet-activating factor antagonist SR 27417, did not modify bronchial hyper-reactivity to SP. Captopril (5 mg/kg i.v.), but not thiorphan (0.8 mg/kg i.v.), increased the SP-induced bronchoconstriction in actively sensitized animals, whereas both inhibitors were equally effective in nonsensitized guinea pigs. Thiorphan, however, did not modify the in vivo response to septide. Our results demonstrate that guinea pigs sensitized to ovalbumin exhibit bronchial hyperreactivity to SP, but not to neurokinin A, as compared to nonsensitized animals, suggesting a decrease in the neutral endopeptidase activity in the airways brought by the immunization. However, the results obtained by using septide indicate that other mechanisms may be involved in the bronchial hyper-reactivity to SP.
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PMID:Effect of active sensitization on the bronchopulmonary responses to tachykinins in the guinea pig. Modulation by peptidase inhibitors. 835 11

Astrocytes play an important role in initiating and modulating inflammatory responses within the central nervous system. Extensive studies in rodents have shown that TPA, substance P, calcium ionophore A21387, and lipopolysaccharide (LPS) induce formation and release of arachidonic acid metabolites which have immunoregulatory properties. To better understand the immunopathology of brain injury, we studied the role of inflammatory cytokines such as tumor necrosis factor alpha, interleukin (IL) 6, IL-2, interferon gamma and IL-1 beta in the production of arachidonic acid metabolites in cells from fetal human brain. Among these cytokines, only IL-1 beta significantly stimulated production of prostaglandins E2 and F2 alpha but not PGD2, thromboxane B2 and 6-keto-PGF1 alpha. Under our experimental conditions, these astrocyte cultures did not produce metabolites in the lipoxygenase pathway such as leukotrienes B4 and C4 upon IL-1 beta stimulation. The stimulatory effects of IL-1 beta on the induction of arachidonic acid metabolites have been studied in various human cell types but not in astrocytes. Human astrocyte production of PGF2 alpha and PGE2 but not PGD2, 6-keto-PGF1 alpha and TXB2 when stimulated by IL-1 beta, is thus a novel finding. This observation should initiate investigations into the mechanism of arachidonic acid metabolism and the role of its metabolites in inflammation in the human nervous system.
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PMID:Recombinant human interleukin 1 beta induces production of prostaglandins in primary human fetal astrocytes and immortalized human fetal astrocyte cultures. 898 97

We have investigated the possible interaction (cross talk) between the phospholipase A2 (PLA2) and inositol 1,4,5-trisphosphate/protein kinase C (PKC) signaling pathways in rat lactotroph-enriched cell cultures. Melittin, a bee venom peptide, stimulated release of [3H]arachidonic acid ([3H]AA) from [3H]AA-labeled enriched lactotrophs in a dose-dependent manner. Moreover, melittin and exogenous AA induced a redistribution of PKC catalytic activity and PKC alpha and beta immunoreactivity from the soluble to the particulate fraction in resting and substance P (SP)-stimulated cells. Melittin had no effect on phospholipase C (PLC) activity. Pretreatment of cell cultures with the PLA2 inhibitors quinacrine and aristolochic acid resulted in a dose-dependent inhibition of melittin-stimulated PKC isozyme translocation as did the inhibitor of lipoxygenase, nordihydroguaiaretic acid, whereas the cyclooxygenase inhibitor indomethacin had no effect. SP and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) dose-dependently increased levels of [3H]AA released from cells. Pretreatment of cell cultures with quinacrine reduced the effect of SP on [3H]AA formation. After long-term treatment (24 h) of cells with TPA, the effect of TPA on [3H]AA production was not different from control, whereas SP still displayed [3H]AA-releasing abilities although not at full scale. Pretreatment of cells with thapsigargin, U 73122, methoxyverapamil, and RHC 80267, an inhibitor of diacylglycerol lipase, all resulted in reduced SP-stimulated [3H]AA liberation. Treatment of cell cultures with pertussis toxin (PTX) reduced the release of [3H]AA induced by SP, whereas PTX had no effect on SP-stimulated generation of 3H-inositol phosphates. On the basis of these results, it is concluded that (1) the PLA2 pathways interfere with the phosphoinositide-PLC signaling system at the level of PKC isozymes alpha and beta, the product responsible for this interaction being either AA or a metabolite produced by the action of lipoxygenase; (2) SP and TPA are able to activate the PLA2 pathway at a level at or beyond PLA2, and this effect is mediated, in part, through PKC alpha and beta species and (for SP) intracellular Ca2+ recruited from internal stores as well as from external sources; and (3) SP also activates PLA2 through a PTX-sensitive pathway distinct from the one coupled to phosphoinositide-PLC, which is PTX insensitive.
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PMID:Cross talk between substance P and melittin-activated cellular signaling pathways in rat lactotroph-enriched cell cultures. 923 37

We investigated a role of neuroregulation in the release of eosinophil chemotactic activity (ECA) from bovine bronchial epithelial cells (BBEC). BBEC were stimulated with acetylcholine (ACh) and substance P (SP), and the supernatant fluids were tested for ECA by a blind-well chemotactic chamber technique. BBEC released ECA in response to ACh and SP in a dose- and time-dependent manner. Checkerboard analysis showed that ECA in regard to ACh and SP was chemotactic rather than chemokinetic. Partial characterization revealed that ECA involved both lipids and peptides. The release of ECA in response to ACh and SP was inhibited by nonspecific and 5-specific lipoxygenase inhibitors and by cycloheximide (P < 0.01). Molecular-sieve column chromatography revealed that these mediators induced three molecular mass peaks (near 25 kDa, 9 kDa, and 400 Da, respectively). The lowest peak, which represented the predominant activity, was blocked by leukotriene B4-receptor antagonist (P < 0. 01) but not by platelet-activating factor-receptor antagonist. The release of leukotriene B4 in the supernatant fluids was increased in response to ACh and SP stimulation (P < 0.01). Platelet-activating factor was not detected. These results raise the possibility of a role of neuroregulation for the elaboration of ECA in the airway.
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PMID:Acetylcholine and substance P stimulate bronchial epithelial cells to release eosinophil chemotactic activity. 957 95

Neurological transmitters including ACh, substance P (SP), and calcitonin gene-related peptide (CGRP) play an important role in regulating airway tone, and increased bronchial reactivity to cholinergic stimulation is a well-recognized phenomenon in patients with bronchial asthma. We postulated that ACh, SP, and CGRP might stimulate alveolar macrophages (AMs) to release neutrophil, monocyte, and eosinophil chemotactic activities. To test this hypothesis, bovine AMs were isolated by bronchoalveolar lavage and cultured. AMs released chemotactic activities in response to ACh in a dose- and time-dependent manner (P < 0.05). However, SP and CGRP did not stimulate bovine AMs. Checkerboard analysis revealed that these released activities were predominantly chemotactic. Partial characterization and molecular-sieve column chromatography revealed that low-molecular-weight lipid-soluble activity was predominant. Lipoxygenase inhibitors significantly blocked the release of chemotactic activities (P < 0.05). Leukotriene B4- and platelet-activating factor-receptor antagonists blocked the chemotactic activities. Immunoreactive leukotriene B4 significantly increased in supernatant fluids in response to ACh (P < 0.05), but platelet-activating factor did not. The receptor responsible for the release of the chemotactic activities was the muscarinic M3 receptor. These data demonstrate that ACh stimulates AMs to release lipoxygenase-derived chemotactic activities and plays a role in inflammatory cell recruitment into the airway.
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PMID:Acetylcholine stimulates alveolar macrophages to release inflammatory cell chemotactic activity. 960 36

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