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)

We investigated the effect of aqueous extract of Soloanum lyratum THUNB. (Solanaceae) (SLAE) on anaphylactic reaction. The mast cell is widely thought to contribute to the acute changes associated with anaphylaxis. SLAE inhibited skin mast cells-mediated anaphylactic reaction activated by anti-dinitrophenyl (DNP) IgE. SLAE dose-dependently inhibited histamine release in mouse peritoneal mast cells activated by anti-DNP IgE or substance P. Substance P increased steady state levels of L-histidine decarboxylase (HDC) mRNA in mouse mastocytoma P-815 cells. Northern-blot analysis demonstrated that significantly reduced level of the mRNA of HDC was expressed in mast cells treated with SLAE, compared to that without SLAE. We conclude that SLAE directly affect IgE-mediated anaphylactic reaction and substance P-induced HDC mRNA over-expression.
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PMID:Solanum lyratum inhibits anaphylactic reaction and suppresses the expression of L-histidine decarboxylase mRNA. 954 4

Calcitonin gene-related peptide (CGRP) and the preprotachykinin A gene-derived peptides substance P (SP) and neurokinin A (NKA) are expressed in extrinsic primary afferent nerve fibres and intrinsic enteric neurons of the gut. The actions of tachykinins on the digestive effector systems are mediated by three different types of tachykinin receptor, termed NK1, NK2 and NK3 receptors, while the gastro-intestinal actions of CGRP are brought about by CGRP1 and possibly other CGRP receptors. These neuropeptide transmitters are expressed by enteric neurons, intestinal muscle, epithelium and vascular system in a cell-specific manner and enable SP, NKA and CGRP to influence motility, electrolyte and fluid secretion, vascular and immune functions in a peptide- and region-specific fashion. Inflammatory disorders of various aetiology involve changes in the peptidergic innervation of the gut, and inflammatory bowel disease is associated with NK1 receptor upregulation in intestinal blood vessels and lymphoid structures. Some of these alterations are reproduced in experimental models of gastro-intestinal disease, and there is mounting evidence that an imbalanced function of peptidergic neurons contributes to motor, secretory, vascular and immunological disturbances in intestinal anaphylaxis, infection and inflammation. In a therapeutic perspective it seems conceivable that tachykinin and CGRP receptors antagonists can be employed as spasmolytic, antidiarrhoeal, anti-inflammatory and antinociceptive drugs.
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PMID:Implications of tachykinins and calcitonin gene-related peptide in inflammatory bowel disease. 969 97

Actively sensitised guinea-pigs were exposed to inhalation challenges with ovalbumin aerosol (macro- and microshock) and airway responsiveness to six intravenously administered spasmogens was evaluated 18 to 24 hr later in the anaesthetised animal. An increase in airway sensitivity was defined as a significant leftward shift of the dose-response curve when compared with saline-challenged control sensitized animals. After ovalbumin-macroshock (1% ovalbumin for 2 min. with mepyramine cover against fatal anaphylaxis), airway hyperresponsiveness was seen to 5-HT, the thromboxane A2-mimetic, U-46619, and bradykinin but not to methacholine, histamine or substance P. A similar pattern was seen after ovalbumin-microshock (0.010% ovalbumin for 60 min.), with induction of airway hyperreactivity to 5-HT and U-46619 but not methacholine or histamine. When the U-46619 dose-response curve was constructed following treatment of the animals with atropine (1 mg/kg, intravenously), airway hyperresponsiveness was no longer significant. As an index of airway inflammation, lung weights were significantly heavier in ovalbumin-challenged animals, than in saline-challenged controls. The results of this study with intravenously administered spasmogens does not support claims that ovalbumin-induced airway hyperreactivity in the guinea-pig is a 'non-specific' phenomenon.
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PMID:Airway hyperresponsiveness in anaesthetised guinea-pigs 18-24 hours after antigen inhalation does not occur with all intravenously administered spasmogens. 1040 30

Anti-scratch effects of oxatomide and epinastine were examined in mice. Scratching behavior and cutaneous reactions were induced in BALB/c, ICR and ddY mice by dinitrofluorobenzene painting, passive cutaneous anaphylaxis and substance P injection, respectively. Although oxatomide and epinastine failed to inhibit scratching behavior in BALB/c mice, they inhibited the cutaneous reaction significantly. The drugs potently inhibited both scratching behavior and cutaneous reaction in ICR mice. They also inhibited scratching behavior and cutaneous reaction in ddY mice, although cetirizine and terfenadine failed to affect them. Histamine did not induce frequent scratching behavior in BALB/c and ddY mice. These results indicate that oxatomide and epinastine inhibit the scratching behavior in ICR mice associated with passive cutaneous anaphylaxis mainly through an antagonistic action on histamine H(1) receptors. The results also indicate that these drugs inhibit substance P-induced scratching behavior in ddY mice through an action independent of the antagonistic action on histamine H(1) receptors.
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PMID:Evaluation of anti-scratch properties of oxatomide and epinastine in mice. 1091 87

Scratching behavior was induced in 12 strains of mice and the frequency was compared. An injection of histamine at a dose of 50 nmol induced frequent scratching behavior only in ICR mice, although the same dose of serotonin induced frequent scratching behavior in all strains of mice except for A/J. Histamine (10 nmol), serotonin (1 nmol), substance P (50 nmol) and passive cutaneous anaphylaxis induced significant vascular permeability increase in BALB/c, ICR, ddY and NC/Nga mice. These four stimuli also induced frequent scratching behavior in ICR mice. However, they failed to induce substantial increase in the incidence of scratching in the other three strains, except for ddY, which exhibited a slight but significant increase against substance P injection. These results suggest that the ICR mouse is a good responder for scratching behavior against various stimuli, especially against histamine. Thus ICR mice may be suitable for studying mediators and/or mechanisms for itching.
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PMID:Scratching behavior in various strains of mice. 1131 67

1 To evaluate the role of prostaglandin I(2) (PGI(2)) in allergic inflammation, allergic responses in the airway, skin and T cells were studied in mice lacking the receptor for PGI(2) (the prostanoid IP receptor) through gene disruption. 2 Three inhalations of antigen caused an increase in plasma extravasation, leukocyte accumulation and cytokine (interleukin (IL)-4 and IL-5) production in the airway of sensitized mice. These airway inflammatory responses were significantly greater in IP receptor deficient mice than in wild-type mice. 3 The vascular leakage caused by passive cutaneous anaphylaxis, substance P and 5-hydroxytryptamine was markedly increased in the skin of IP receptor deficient mice, compared with comparably treated wild-type mice. 4 The inhalation of antigen in sensitized mice resulted in increased serum antigen specific IgE, total IgE and IgG levels. The magnitude of the elevations of each immunoglobulin level in IP receptor deficient mice is notably higher than that in wild-type mice. To elucidate the mechanism of an enhancement of immunoglobulin production, the activity of T cells in sensitized and non-sensitized mice was studied by means of the production of cytokines. The antigen-induced IL-4 production by spleen cells from sensitized IP receptor deficient mice was almost three times greater than that in wild-type mice. On the contrary, the anti-CD3 antibody-induced interferon-gamma production by CD4(+) T cells from non-sensitized IP receptor deficient mice was significantly lower than that in wild-type mice. 5 The present data indicate that IP receptor deficiency reinforced an allergic airway and skin inflammation by augmentation of vascular permeability increase and the T helper 2 cell function. These findings suggest a regulatory role of PGI(2) in allergic inflammation.
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PMID:Augmentation of allergic inflammation in prostanoid IP receptor deficient mice. 1223 50

Slow-reacting substance produced in anaphylaxis (SRS-A) increased resistance of the lungs to inflation in the guinea-pig in vivo and caused isolated preparations of its tracheobronchial muscle to contract. SRS-A also contracted human isolated bronchial muscle and some but not all preparations of rabbit trachea. Nonsteroid anti-inflammatory drugs, which antagonize bronchoconstriction induced by kinins, but not that by histamine, acetylcholine, 5-hydroxytryptamine, substance P, angiotensin or lung prostaglandin, also antagonized the bronchoconstrictor action of SRS-A. This antagonism resembled that of kinins in being surmounted by higher doses of agonist, in the potencies of active drugs and in the types of drugs which were inactive. However, receptors in guinea-pig tracheobronchial muscle for SRS-A seem to be distinct from those for bradykinin, since preparations of this muscle could become unresponsive to either agent in vivo and in vitro, while remaining responsive to the other.
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PMID:BRONCHOCONSTRICTOR ACTION AND ANTAGONISM OF A SLOW-REACTING SUBSTANCE FROM ANAPHYLAXIS OF GUINEA-PIG ISOLATED LUNG. 1420 95

Urticaria and angioedema are common allergic manifestations and medications are one of common triggering factors. The most severe immediate drug reaction is anaphylaxis. Apart from the well established IgE-mediated immediate type hypersensitivity reactions, the pathogenesis of drug-induced urticaria, angioedema and anaphylaxis often remains obscure. In this article, emphasis is put on nonallergic reactions to the most commonly used drug groups of nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, radiocontrast media, volume expanders and drugs used in general anesthesia. Urticaria is the second most common drug eruption after maculopapular exanthema. The mechanisms of acute urticarial reactions are multiple, mostly IgE mediated, but some drugs can induce immune complex reactions and activate complement cascade, while others can induce direct activation of mast cells and degranulation or activation of complement by non-immune mechanisms. With different types of medications different pathomechanisms are involved. Non-steroid anti-inflammatory drugs are thought to cause reaction due to cyclooxygenase-1 inhibition and overproduction of leukotrienes, blamed for cutaneous and respiratory symptoms. Angiotensin-converting enzyme inhibitors can cause fatal angioedema, which is partially explained with bradykinin excess and impairment of aminopeptidase P and dipeptidyl peptidase IV that are involved in the metabolism of substance P and bradykinin. It remains unknown what additional mechanisms are involved. Radiocontrast media and local anesthetics mostly cause nonallergic hypersensitivity reaction, but in rare cases true allergic reaction can occur. Dextran is known to cause IgG mediated, immune complex anaphylaxis and it is recommended to use human serum albumin as the safest colloid.
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PMID:Nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, radiocontrast media, local anesthetics, volume substitutes and medications used in general anesthesia. 1938 16

We present a case of a 75-year-old woman treated with an ACE inhibitor, who presented with angio-oedema of the tongue and had difficulty speaking. No symptoms of anaphylaxis or urticaria were present. The patient was treated intravenously with antihistamine and glucocorticoid in combination with adrenaline inhalations. After 6 h in the hospital the swelling progressed, and the patient was admitted to the intensive care unit and treated with one injection of icatibant-a bradykinin receptor antagonist. The patient reported subjective relief after 20-30 min and the swelling resolved within 2 h. Although the angio-oedema was potentially life threatening, the patient avoided intubation and mechanical ventilation. ACE inhibitor-induced angio-oedema is most likely caused by an accumulation of bradykinin and substance P. Consequently, a bradykinin receptor antagonist is the rational treatment of choice instead of antiallergic medications, which have no proven efficacy in this condition.
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PMID:Life-threatening ACE inhibitor-induced angio-oedema successfully treated with icatibant: a bradykinin receptor antagonist. 2649 71

To examine pharmacologic and clinical characteristics of neurokinin 1 (NK1)-receptor antagonists (RAs) for preventing chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy, a literature search was performed for clinical studies in patients at risk of CINV with any approved NK1 RAs in the title or abstract: aprepitant (capsules or oral suspension), HTX019 (intravenous [IV] aprepitant), fosaprepitant (IV aprepitant prodrug), rolapitant (tablets or IV), and fixed-dose tablets combining netupitant or fosnetupi-tant (IV netupitant prodrug) with the 5-hydroxytryptamine type 3 (5HT3) RA palonosetron (oral or IV). All NK1 RAs are effective, but exhibit important differences in efficacy against acute and delayed CINV. The magnitude of benefit of NK1-RA-containing three-drug vs two-drug regimens is greater for delayed vs acute CINV. Oral rolapitant has the longest half-life of available NK1 RAs, but as a consequence should not be administered more frequently than every 2 weeks. In general, NK1 RAs are well tolerated; however, IV rolapitant was recently removed from US distribution, due to hypersensitivity and anaphylaxis, and IV fosaprepitant is associated with infusion-site reactions and hypersensitivity presumed related to its polysorbate 80 excipient. Also, available NK1 RAs have potential drug-drug interactions. Adding an NK1 RA to 5HT3 RA and dexamethasone significantly improves CINV control vs the two-drug regimen. Newer NK1 RAs offer more formulation options, higher acute-phase plasma levels, or improved tolerability, and increase clinicians' opportunities to maximize benefits of this important class of antiemetics.
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PMID:Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and vomiting. 3032 22


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