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)

Chronic exposure of rats to high concentrations of SO2 gas induces a syndrome similar to human chronic bronchitis. The aim of these studies was to determine if substance P (SP) content in the trachea or lungs was elevated in this animal model of chronic bronchitis, and whether an increase in SP content was associated with an increase in preprotachykinin gene-I (PPT) mRNA expression. Rats were exposed to air (controls) or 250 ppm SO2 gas, 5 h per day, 5 days per week, for a period of 4 wk. Animals were killed and the lungs and trachea were frozen in liquid nitrogen for measurement of SP content by enzyme-linked immunosorbent assay. The SP content of the tracheas from SO2-exposed rats was 3-fold greater than controls (8.9 +/- 1.2 and 3.0 +/- 0.7 pmol/g tissue, respectively; P=0.0005), whereas the SP content of the lungs was not different (SO2 = 4.8 +/- 0.8 and air = 3.0 +/- 0.7 pmol/g tissue, respectively; P = 0.06). In order to determine whether SP synthesis in the cell bodies of the C-fibers innervating the trachea and lungs accompanied a change in SP levels, thoracic dorsal root ganglia and nodose ganglia were removed and PPT mRNA quantitated by Northern analysis. There was no difference in PPT mRNA between control and SO2-exposed rats in nodose or dorsal root ganglia. These results suggest a post-transcriptional mechanism of PPT regulation. Elevated SP levels could play a protective role in the responses of the airways to chronic exposure of inhaled irritants.
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PMID:Substance P content and preprotachykinin gene-I mRNA expression in a rat model of chronic bronchitis. 860 Sep 37

To investigate the role of tachykinin release in mediating the bronchoconstrictive effect of sulfur dioxide (SO2) inhalation, measurements of dynamic lung compliance (Cdyn), total pulmonary resistance (RL), and arterial blood pressure (ABP) were made in anesthetized guinea pigs. Brief exposure (six tidal breaths) to SO2 at concentrations between 500 and 2,000 parts/million resulted in a concentration-dependent increase in RL, decrease in Cdyn, and systemic hypotension. For example, SO2 at 2,000 parts/million induced reversible and reproducible changes in RL, Cdyn, and ABP of 1,041 +/- 234, -60 +/- 6, and -25.8 +/- 4.3% of the baseline values, respectively. Pretreatment with two selective neurokinin- (NK) receptor (NK1 and NK2) antagonists, CP-99994 and SR-48968, resulted in almost complete inhibition of the increase in RL and of the decrease in Cdyn while preserving the decrease in ABP. Antagonism of the NK2 receptor alone resulted in inhibition of the majority of the SO2-induced bronchoconstriction, whereas that of the NK1 and muscarinic receptors did not have a significant effect. We conclude that the release of tachykinins from sensory endings plays a central role in SO2-induced bronchoconstriction in anesthetized guinea pigs, primarily via the activation of the NK2 receptor.
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PMID:Role of tachykinins in sulfur dioxide-induced bronchoconstriction in anesthetized guinea pigs. 880 12

In the present investigation a possible involvement of tachykinins during sulfur dioxide-(SO2) and metabisulfite-(MBS) induced bronchoconstriction, and paraquat (PQ)-induced mortality was studied. SO2 (250ppm) inhalation and MBS (3mM) perfusion induced a marked decrease of compliance and conductance in the isolated and perfused lung. SO2-induced bronchoconstriction was associated with release of Calcitonin Gene Related Peptide, suggesting activation of capsaicin sensitive sensory nerves. Pretreatment of animals with capsaicin, in order to deplete the tachykinin content of sensory nerves, significantly reduced SO2- and MBS-induced bronchoconstriction. PQ (25mg/Kg) treatment induced high mortality (75%) after 3 weeks. Pretreatment with capsaicin significantly protected versus PQ induced mortality (25%). The results suggest that tachykinin content in the respiratory airways participate to SO2- and MBS-induced bronchoconstriction and PQ mortality.
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PMID:[Participation of tachykinins in experimental models of lung damage]. 899 27

Inhalation of sulphur dioxide (250 ppm), (SO2) or sodium metabisulfite (80 mM) (MBS) aerosol or perfusion with MBS (3 mM) induced a reduction in compliance and conductance in the isolated, perfused and ventilated guinea pig lung. Pretreatment of the lung with sodium sulfite (3 mM), a dissolution product of SO2 and MBS, reduced the bronchoconstriction induced by SO2 and MBS. Bronchoconstriction induced by SO2 and MBS in associated to increased levels of Calcitonin gene-Related Peptide (CGRP) in the perfusate effinent, indicating activation of sensory nerves. The release of CGRP induced by SO2 and MBS was not affected by sodium sulfite. Sulfite treatment did not modify lung reactivity towards acethylcholine, bradykinin, serotonin, histamine and substance P (fragment 5-11). An inhibitory effect by sulfite was observed on bronchoconstriction induced by neurokinin A (fragment 4-10). Since bronchoconstriction induced by SO2 and MBS appears to be mediated by neurokinin A release and action, sulfite may act by affecting its signal transduction pathway. In conclusion, the results indicate that during exposure to some environmental and occupational pollutants, e.g. SO2 and MBS, critical modifications of sulfhydryl groups on smooth muscle receptors may occur. We hypothesise this as a possible step in the development of tolerance and hyperreactivity.
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PMID:[Mechanisms of tolerance to sulfur dioxide and sodium metabisulfite]. 937 46

The upper airway occupies a sentinel position with respect to the physical and chemical qualities of the inspired atmosphere. Responses of the upper airway can be acute or chronic, as well as primary (sensory) or secondary (physiologic). Olfaction and sensory irritation are cofactors in the perception of air quality. Secondary reflex responses to airborne irritants may include blockage (airflow obstruction), secretion (with or without associated inflammation), and alterations in mucociliary clearance. Of the above end points, obstruction has been documented in response to a variety of agents, including acetic acid vapor, ammonia, Cl2, ETS, mixed VOCs, vapors from carbonless copy paper, and (variably) SO2. Alterations in mucociliary clearance have been variably observed with SO2 and ETS exposure. A neutrophilic inflammatory response has been documented after acute exposure to either ozone or VOCs, and metaplastic mucosal changes after prolonged exposures to photochemical mixed air pollutants. Augmented reactivity to irritants is a phenotypic characteristic of both nonallergic and allergic rhinitis; however, understanding of underlying mechanisms remains elusive (75-78). Differential physiologic responsiveness to environmental irritant stimuli has been documented by allergic rhinitis status for acetic acid and Cl2 (objectively) and for mixed VOCs (subjectively only). Differential responsiveness by nonallergic rhinitis status has, to our knowledge, been documented for paper dust only, although a somewhat wider array of pollutants (including ETS and carbonless copy paper) has been studied in groups differing by self-reported pollutant reactivity. Interestingly, although the congestive response to allergens and irritants is similar, the underlying mechanisms appear to differ, with neither mast cell degranulation nor cholinergic parasympathetic reflexes appearing critical to the response (Fig. 3). Although neuropeptide release does not accompany Cl2-induced nasal obstruction, in one model system (hypertonic saline challenge), substance P release accompanied augmented secretions (80,81). In yet another hypertonic model (dry mannitol powder challenge), arachidonic acid metabolites characteristic of epithelial cell activation accompanied nasal obstruction (82). The relevance of these model systems to environmentally realistic (airborne) irritants remains unclear at this time. Overall, nonallergic rhinitis has received considerably less attention than has allergic rhinitis in the context of descriptive, pathophysiologic, and intervention studies. This statement applies equally in the context of environmental nonallergic rhinitis. As is hopefully evident from the above discussion, many potential research questions in this area remain to be addressed.
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PMID:Environmental nonallergic rhinitis. 1715 18