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)

Neuroendocrine components exist in the human nasal mucosa. However, the pathophysiological and neuroimmunological roles of the regulatory peptides in allergic rhinitis (AR) require further investigation. To analyse the functional morphology and quantify the tissue concentration of regulatory peptides in the nasal mucosa of AR subjects, human inferior turbinate mucosa specimens from 25 patients with AR, 20 patients with non-allergic rhinitis and 10 patients without any nasal diseases were investigated. Using immunohistochemistry and radioimmunoassays, we detected the presence, distribution and concentrations of various neuropeptides [vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P (SP) and calcitonin gene-related peptide (CGRP)] and general neuroendocrine markers (neuron-specific enolase and chromogranin A). Quantitative analysis of the stained fibres and cells was performed using a graphic AutoCAD program. The presence and distribution of NPY, CGRP and SP nerve fibres and neuroendocrine cells were similar among the three subject groups. AR subjects had significantly higher tissue concentrations of VIP and SP. AR subjects had increased numbers of VIP fibres which predominantly innervated vessels. Thus, VIP and SP play important neuroimmunological roles in the pathogenesis of AR.
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PMID:Distribution and quantity of neuroendocrine markers in allergic rhinitis. 965 16

In this in vivo prospective, controlled study, we have examined the capsaicin-induced levels and secretion patterns of the colocalized neuropeptides substance P, calcitonin gene-related peptide (CGRP), and neurokinin A in nasal secretions of subjects with nasal polyps, and we compared these with secretion patterns from healthy subjects and from subjects with allergic rhinitis. Capsaicin was used to elicit neuropeptide release. The neuropeptide levels were measured by an ELISA technique. For substance P, subjects with nasal polyps responded very poorly to capsaicin stimulation. The atopic group was more reactive to capsaicin stimulation than control subjects. For CGRP the increase was immediate in all groups. Atopic subjects and subjects with polyps had a less pronounced but sustained response to capsaicin stimulation. CGRP levels in atopic subjects and those with polyps were restored rapidly. Atopic subjects had higher neurokinin A levels with an immediate and sustained response to capsaicin. Control subjects had higher levels than those with polyps, but both groups were nonresponsive to capsaicin stimulation.
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PMID:Decreased neuropeptide release may play a role in the pathogenesis of nasal polyps. 1054 75

Levocabastine is a selective histamine H1-receptor antagonist exerting inhibitory effects on the release of chemical mediators from mast cells and on the chemotaxis of polymorphonuclear leukocytes and eosinophils. Both histamine and antigens induced conjunctivitis was inhibited by levocabastine in several allergy models. Levocabastine moderately inhibited histamine-release from guinea pig conjunctive induced by antigen-antibody reactions and prevented an increase in the vascular permeability of the conjunctive elicited by both histamine and antigen instillation. Symptoms of allergic rhinitis, which were induced by histamine, substance P and antigen, were also reduced by levocabastine. Levocabastine prevented an increase in the vascular permeability of nasal mucosa elicited by instillation of these three inducers. Furthermore, levocabastine has shown a large difference between the antiallergic dose and other non-specific pharmacological effective dose than that with other antiallergic drugs. The non-specific pharmacological effect of levocabastine reveals only blepharoptosis. With these pharmacological effects and topical usage, levocabastine was shown to be useful for allergic conjunctive and rhinitis in both seasonal and perennial clinical use.
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PMID:[Pharmacological and clinical properties of levocabastine hydrochloride (eye drop and nasal spray), a selective H1 antagonist]. 1191 20

Stimulation of the nasal sensory nerves leads to sensations of pain and stuffiness. Type C nociceptive nerve releases neuropeptides including substance P and calcitonin gene related peptides that increase plasma extravasation and glandular secretion. This axonal response acts as an immediate protective mucosal defense mechanism. Recruited parasympathetic reflexes cause submucosal gland secretion via acetylcholine and muscarinic M(3) receptors. Itching, sneezing, and other avoidance behaviors rapidly clear the offending agents from the upper airways and protect the lower airways. Dysfunction of these nerves may contribute to allergic rhinitis, infectious rhinitis, nasal hyperresponsiveness, and possibly sinusitis. Sympathetic arterial vasoconstriction reduces mucosal blood flow, sinusoidal filling, and mucosal thickness, and so restores nasal patency. Loss of sympathetic tone may contribute to some chronic, nonallergic rhinopathies. Human axon responses differ from those in animals, an important distinction that limits extrapolation from other species.
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PMID:Upper airway neurogenic mechanisms. 1196 45

Computer-induced stress enhanced allergen-specific skin wheal responses in patients with atopic dermatitis (AD) while it failed to do so in patients with allergic rhinitis (AR). Computer-induced stress also enhanced plasma levels of substance P (SP) and vasoactive intestinal peptide (VIP) in patients with AD, but not with AR. Peripheral blood mononuclear cells stimulated with combination of IL-4, IL-10, anti-CD40 mAb, and allergen produced allergen-specific IgE production in both patients with AD and AR. Computer-induced stress enhanced allergen-specific IgE production by peripheral blood mononuclear cells from patients with AD, but not from patients with AR. This is the first report that computer-induced stress enhances allergen-specific responses with concomitant increase of plasma levels of SP and VIP specifically in patients with AD. Since AD is often aggravated by stress, these finding may have implications for the pathophysiology and treatment of AD.
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PMID:Enhancement of allergic skin wheal responses and in vitro allergen-specific IgE production by computer-induced stress in patients with atopic dermatitis. 1267 75

Angiotensin-converting enzyme (ACE) inactivates bradykinin, substance P, and neurokinin A, which are thought to play important roles in the pathogenesis of inflammatory diseases. Expression of angiotensinogen, a precursor of angiotensin, is enhanced by augmented secretion of proinflammatory cytokines (eg, interleukin-1) in the site of inflammation. Insertion or deletion (I/D) ACE and M235T angiotensinogen gene polymorphisms were reported to be associated with atopy in a Czech population. Using polymerase chain reaction restriction fragment length polymorphism and SNaPshot typing analysis, we investigated the frequencies of the genotypes and alleles of the ACE gene in 137 patients with allergic rhinitis, of the M235T angiotensinogen gene in 186 patients with allergic rhinitis, and of both in 219 healthy control subjects. There was no difference in the frequency of the DD genotype of the ACE gene in the controls and patients (odds ratio, 1.32 [0.66-2.60]; p > .05). The D allele was more frequent in patients, but the difference was not statistically significant (odds ratio, 1.21 [0.89-1.64]; p > .05). There was no difference in the frequency of the TT genotype of the angiotensinogen gene in the controls and patients (odds ratio, 1.01 [0.38-2.69]; p > .05). The T allele was more frequent in patients, but the difference was not statistically significant (odds ratio, 1.10 [0.78-1.55]; p > .05). Our results indicate that polymorphisms in the genes for ACE and angiotensinogen may not be related to the development of allergic rhinitis in the Korean population.
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PMID:Association between polymorphisms of the angiotensin-converting enzyme and angiotensinogen genes and allergic rhinitis in a Korean population. 1511 73

The diffuse neuroendocrine system consists of specialised endocrine cells and peptidergic nerves and is present in all organs of the body. Substance P (SP) is secreted by nerves and inflammatory cells such as macrophages, eosinophils, lymphocytes, and dendritic cells and acts by binding to the neurokinin-1 receptor (NK-1R). SP has proinflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems. Many substances induce neuropeptide release from sensory nerves in the lung, including allergen, histamine, prostaglandins, and leukotrienes. Patients with asthma are hyperresponsive to SP and NK-1R expression is increased in their bronchi. Neurogenic inflammation also participates in virus-associated respiratory infection, non-productive cough, allergic rhinitis, and sarcoidosis. SP regulates smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function in the gastrointestinal tract. Elevated levels of SP and upregulated NK-1R expression have been reported in the rectum and colon of patients with inflammatory bowel disease (IBD), and correlate with disease activity. Increased levels of SP are found in the synovial fluid and serum of patients with rheumatoid arthritis (RA) and NK-1R mRNA is upregulated in RA synoviocytes. Glucocorticoids may attenuate neurogenic inflammation by decreasing NK-1R expression in epithelial and inflammatory cells and increasing production of neutral endopeptidase (NEP), an enzyme that degrades SP. Preventing the proinflammatory effects of SP using tachykinin receptor antagonists may have therapeutic potential in inflammatory diseases such as asthma, sarcoidosis, chronic bronchitis, IBD, and RA. In this paper, we review the role that SP plays in inflammatory disease.
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PMID:The role of substance P in inflammatory disease. 1533 52

Tachykinins are neuropeptides which regulate various biological responses, some of which are potentially important in the pathogenesis of pulmonary diseases such as asthma. Tachykinins produce their biological effects by stimulating specific tachykinin receptors (NK(1), NK(2) and NK(3)). Tachykinins have a variety of effects in the lungs. They are among the most potent bronchoconstrictor agents known and have potent effects on airway blood vessel caliber, causing vasodilation by an endothelium-dependent mechanism. Exogenously administered tachykinins (substance P, neurokinin A and neurokinin B) induce mucus secretion in most species, including humans. In addition to having effects on airway secretion, tachykinins also modulate the mucociliary clearance mechanisms of the airway. Tachykinin receptors are found on pulmonary/bronchial C fibers, and both excitatory and inhibitory effects of tachykinins on neural discharge and neurotransmitter release from these nerves have been described. Tachykinins are also involved in several reflex responses, particularly the cough reflex. Tachykinins have been implicated in the inflammatory response in the lungs and they also participate in the regulation of the immune system. A considerable body of evidence implicates tachykinins as important mediators of the neurogenic inflammatory response in a variety of pulmonary diseases. It is thus expected that tachykinin receptor antagonists will prove useful in the therapy of diseases such as asthma, allergic rhinitis and chronic bronchitis.
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PMID:Tachykinins in the lungs. 1561 76

To evaluate the effect of cetirizine hydrochloride on substance P release in allergic rhinitis, we performed a single-blind placebo-controlled study of 14 patients with perennial allergic rhinitis (7 treated with cetirizine and 7 with placebo). After an initial nasal allergen challenge with lavages, the subjects received treatment with placebo or cetirizine hydrochloride (10 mg by mouth daily) for 1 week, followed by the second nasal allergen challenge with lavages. The levels of albumin, histamine, and substance P in nasal lavages before and after allergen challenge were quantified by enzyme-linked immunosorbent assay. Pretreatment of subjects with cetirizine reduced the level of substance P induced by antigen challenge, but did not significantly reduce levels of histamine. These results suggest that cetirizine may reduce nasal neurogenic inflammation by modulating the release of substance P in allergic rhinitis.
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PMID:Effects of cetirizine on substance P release in patients with perennial allergic rhinitis. 1563 94

The tachykinins, substance P (SP) and neurokinin A (NK-A), are thought to be key players in the process of neurogenic inflammation, which is believed to contribute to the pathogenesis of various respiratory diseases. Due to the additive nature of the respiratory effects of these sensory neuropeptides, inhibiting the effects of tachykinins at both NK1 and NK2 receptors may represent a therapeutic advantage for the treatment of asthma, as opposed to receptor-selective antagonists, which have demonstrated only minimal efficacy to date. A number of companies are pursuing small molecule approaches yielding compounds with potent, balanced NK1 and NK2 receptor antagonist activities. In allergic rhinitis, NK1 receptor antagonism may complement the actions of antihistamines by addressing nasal congestion, which is largely unrelieved by these otherwise highly efficacious agents. Novel combined H1/NK1 receptor antagonists have been developed and may represent a therapeutic option for the treatment of this disease.
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PMID:Combined tachykinin receptor antagonists for the treatment of respiratory diseases. 1599 15


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