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)

The tachykinin neuropeptides substance P and neurokinin (NK) A have been postulated to participate in the inflammatory reaction in airways of smokers and asthmatics. We have examined the hypothesis that the expression of one or more of the three cloned tachykinin receptors (NK1, NK2, and NK3) is increased in inflammatory airway disorders, which could result in augmentation of the effect of released tachykinin neuropeptides. NK1 receptor and NK2 receptor but not NK3-receptor mRNA were detected by ribonuclease protection assay in RNA from both cartilaginous and membranous bronchi and subpleural lung. In lung samples containing membranous airways, NK2-receptor mRNA expression was increased fourfold in asthmatics compared with nonsmoking controls, whereas NK1-receptor mRNA levels were similar in the two groups. NK1- and NK2-receptor mRNA expression was increased twofold in smokers without airflow obstruction compared with nonsmokers, whereas NK1-receptor mRNA expression was significantly lower in patients with chronic obstructive pulmonary disease compared with smoking controls. In situ hybridization indicated NK1-receptor mRNA was expressed in submucosal glands and airway epithelial cells, whereas NK2-receptor and NK3-receptor mRNA were not detected. These observations have implications for the pathophysiology and treatment of both asthma and tobacco smoke-induced airway inflammation.
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PMID:Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in inflammatory airway diseases. 757 63

An immunohistochemically distinct zone was identified in the superficial aspect of trigeminal nucleus caudalis of the New World owl monkey that is not immunoreactive for substance P or serotonin, in stark contrast to the dense staining present in the surrounding laminae I and II. Thionin-stained sections in different planes showed that this is a subregion of lamina I containing clusters of neurons that appear to have pyramidal or polygonal somata. Extracellular microelectrode recordings in this region revealed clusters of thermoreceptive-specific (COLD) cells with nasal or labial receptive fields, whereas nociceptive neurons were found in the adjacent portions of lamina I. Anterograde tracer injections in this region produced trigeminothalamic terminal labeling in the site homologous to the lamina I spino-thalamo-cortical relay nucleus identified previously in the Old World macaque monkey and in humans. Retrograde tracer injections involving this thalamic site, where recordings of trigeminal COLD-like neurons were obtained, produced clusters of retrogradely labeled trigeminothalamic neurons in this immunohistochemically distinct subregion of lamina I, nearly all of which are pyramidal neurons. We conclude that the nocturnal owl monkey has a specialized perinasal thermoreceptive trigeminothalamic sensory pathway that is probably of behavioral significance during olfactory sniffing. In addition, these observations corroborate other findings that have indicated that lamina I COLD cells are pyramidal neurons and are not physiologically modulated by substance P or serotonin, in contrast to nociceptive neurons.
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PMID:A distinct thermoreceptive subregion of lamina I in nucleus caudalis of the owl monkey. 993 96

The airway innervation consists of a cholinergic system, an adrenergic system, and a non-adrenergic, non-cholinergic (NANC) system. Anticholinergic drugs have long since been used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). The new anticholinergic drug, tiotropium bromide, causes long-lasting bronchodilatation (> or = 24 h) in patients with COPD. The sensory airway neuropeptides, substance P (SP) and neurokinin A (NKA), are potent contractors of smooth muscle, vasodilators and have important proinflammatory effects. Their airway effects are mediated by tachykinin NK1 and NK2 receptors. Antagonists for these receptors are currently being developed as a possible treatment of obstructive airway diseases.
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PMID:Potential usefulness of inhibiting neural mechanisms in asthma. 1121 80

The tachykinins substance P and neurokinin A are contained within sensory airway nerves. Immune cells form an additional source of tachykinins in inflamed airways. Elevated levels of tachykinins have been recovered from the airways of patients with asthma and chronic obstructive pulmonary disease. Airway inflammation leads to an upregulation of tachykinin NK(1) and NK(2) receptors. Preclinical studies have indicated a role for the tachykinin NK(1), NK(2) and NK(3) receptors in bronchoconstriction, airway hyperresponsiveness and airway inflammation caused by allergic and nonallergic stimuli. Compounds that are able to block two or three tachykinin receptors hold promise for the treatment of airways diseases such as asthma and/or chronic obstructive pulmonary disease.
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PMID:Airway inflammation and tachykinins: prospects for the development of tachykinin receptor antagonists. 1169 44

Several lines of evidence indicate a role for the tachykinin peptides in airways diseases. For instance, elevated levels of tachykinins have been recovered from the airways of patients with asthma and chronic obstructive pulmonary disease (COPD), and airway inflammation leads to an upregulation of the tachykinin NK1 and NK2 receptors. Recent advances in tachykinin receptor pharmacology have allowed a more detailed analysis of this system and preclinical animal studies have indicated a role for the NK1 and NK2 receptors in bronchoconstriction, airway hyperresponsiveness and airway inflammation caused by allergic and nonallergic stimuli. In the past three years, work has entered the clinic and selective or dual-selective NK1/NK2 receptor antagonists appear to have the potential to affect the different aspects of asthma and COPD.
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PMID:Tachykinin receptor antagonists: potential in airways diseases. 1171 45

Autonomic innervation of the airways is derived primarily from the parasympathetic nervous system. Preganglionic fibers originating in the brainstem project to parasympathetic ganglion neurons, which regulate airway smooth-muscle tone, glandular secretion and blood-vessel diameter. Airway preganglionic nerve activity is regulated by subsets of pulmonary and extrapulmonary afferent nerve fibers, which continuously provide polysynaptic input to brainstem preganglionic nuclei. Each of these synapses in the central nervous system is a potential site for therapeutic intervention. Potential targets include increasing opioid, GABAergic and serotonergic controls on central neurons, and blockade of tachykinin and glutamate receptors. Unfortunately, much is still unknown about the control of airway nerves at the level of the central nervous system. Recently, however, interaction between vagal afferent nerve subtypes regulating airway function has been described. This interaction, made possible by their convergence at key sites of integration in the brainstem, may lead to central sensitization analogous to that described in somatic pathways regulating pain sensation. Improved understanding of the central pharmacology of airway reflexes may provide novel therapeutics for treating symptoms associated with respiratory disorders such as chronic obstructive pulmonary disease, asthma and sleep-disordered breathing.
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PMID:Central nervous system control of the airways: pharmacological implications. 1202 Apr 61

Experiments were performed to characterize the pharmacology of SCH 206272 [(R,R)-1'[5-[(3,5-dichlorobenzoyl)methylamino]-3-(3,4-dichlorophenyl)-4(Z)-(methoxyimino)pentyl]-N-methyl-2-oxo-[1,4'bipiperidine]-3-acetamide] as a potent and selective antagonist of tachykinin (NK) NK(1), NK(2), and NK(3) receptors. SCH 206272 inhibited binding at human tachykinin NK(1), NK(2), and NK(3) receptors (K(i) = 1.3, 0.4, and 0.3 nM, respectively) and antagonized [Ca(2+)](i) mobilization in Chinese hamster ovary (CHO) cells expressing the cloned human tachykinin NK(1), NK(2), or NK(3) receptors. SCH 206272 inhibited relaxation of the human pulmonary artery (pK(b) = 7.7 +/- 0.3) induced by the tachykinin NK(1) receptor agonist, [Met-O-Me] substance P and contraction of the human bronchus (pK(b = 8.2 +/- 0.3) induced by the tachykinin NK(2) receptor agonist, neurokinin A. In isolated guinea pig tissues, SCH 206272 inhibited substance P-induced enhancement of electrical field stimulated contractions of the vas deferens, (pK(b = 7.6 +/- 0.2), NKA-induced contraction of the bronchus (pK(b) = 7.7 +/- 0.2), and senktide-induced contraction of the ileum. In vivo, oral SCH 206272 (0.1-10 mg/kg, p.o.) inhibited substance P-induced airway microvascular leakage and neurokinin A-induced bronchospasm in the guinea pig. In a canine in vivo model, SCH 206272 (0.1-3 mg/kg, p.o.) inhibited NK(1) and NK(2) activities induced by exogenous substance P and neurokinin A. Furthermore, in guinea pig models involving endogenously released tachykinins, SCH 206272 inhibited hyperventilation-induced bronchospasm, capsaicin-induced cough, and airway microvascular leakage induced by nebulized hypertonic saline. These data demonstrate that SCH 206272 is a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist. This compound may have beneficial effects in diseases thought to be mediated by tachykinins, such as cough, asthma, and chronic obstructive pulmonary disease.
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PMID:SCH 206272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist. 1220 58

Mucus hypersecretion is a prominent feature of chronic inflammatory diseases of the airways, including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis, but little is known about the effects of current therapies for airway disease because of the difficulties in quantifying mucus hypersecretion in clinical studies. Anticholinergics may reduce mucus hypersecretion, whereas beta2 agonists and mucolytics have little obvious effect. Corticosteroids are highly effective in inhibiting mucus hypersecretion in asthma by suppressing the underlying inflammatory process, but are ineffective in COPD and cystic fibrosis. Novel approaches in the future may include inhibition of sensory neuropeptides by tachykinin antagonists, modulators of sensory nerves or K+ channel openers. Inhibition of Th2 cytokines (interleukin [IL]4, IL9, IL13) may also be effective in asthma. In COPD inhibition of neutrophil-derived proteases by small molecule inhibitors or inhibiting neutrophilic inflammation in the airways by reducing neutrophil chemotaxis may also be effective strategies. Several novel targets involved in mucus hypersecretion have recently been identified, including epidermal growth factor receptors, MARCKs, Ca2+-activated Cl- channels and mitogen-activated protein kinases. However, the clinical benefits from inhibiting mucus hypersecretion are still not certain, casting some doubts on this therapeutic approach.
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PMID:Current and future therapies for airway mucus hypersecretion. 1256 98

The tachykinins substance P and neurokinin A are found within airway nerves and immune cells. They have various effects on the airways that can contribute to the changes observed in asthma and chronic obstructive pulmonary disease. Both tachykinin NK(1) and NK(2) receptors have been involved in the bronchoconstriction and the proinflammatory changes induced by substance P and neurokinin A. Tachykinin NK(1) and NK(2) receptor antagonists have activity in various animal models of allergic asthma and chronic bronchitis. It is suggested that dual NK(1)/NK(2) and triple NK(1)/NK(2)/NK(3) tachykinin receptor antagonists have potential in the treatment of obstructive airway diseases.
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PMID:The role of neural inflammation in asthma and chronic obstructive pulmonary disease. 1279 61

The role of tachykininis in airway inflammation has been extensively demonstrated in experimental animal models, but evidence in humans is very sparse. The aim of this study was first to quantify the content of substance P (SP) in sputum of a group of patients, with chronic obstructive pulmonary disease and with exposure to occupational irritants. Secondly, to compare them with sputum SP content of a group of control subjects.
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PMID:[Substance P in the sputum of patients with chronic obstructive pulmonary disease and occupational exposure to respiratory irritants]. 1497 14


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