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 role of neuropeptides in nasal allergy was examined in guinea pigs by histochemical and pharmacological study. Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like behaviors: sneezing and watery rhinorrhea, and decreased histamine content in the nasal mucosa in guinea pigs sensitized with TDI. The immunoreactivity of substance P (SP) and calcitonin gene-related peptide (CGRP) in the nerve terminals in the nasal mucosa was increased after intranasal application of TDI. We also observed a decrease in the immunoreactivity of SP and CGRP, and an increase in their mRNA expression in the trigeminal ganglion neurons. These findings indicate that exposure to TDI enhanced the biosynthesis of both SP and CGRP in the trigeminal ganglion neurons and their axonal transportation to the terminals in the nasal mucosa. In animals pretreated with capsaicin before sensitization, TDI did not induce nasal allergy-like behaviors and histamine release in the nasal mucosa. Since capsaicin depletes SP and CGRP in the sensory nerves, this finding indicates neuropeptide-mediated histamine release in the nasal mucosa. All these findings suggest that, on exposure to TDI, the antidromic release of SP and CGRP in the nasal mucosa triggers the release of histamine, resulting in the development of symptoms of nasal allergy.
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PMID:Neurogenic inflammation in nasal allergy: histochemical and pharmacological studies in guinea pigs. A review. 768 May 20

Effects of capsaicin on autonomic nerves in the nasal mucosa and olfactory bulb of toluene diisocyanate sensitized guinea pigs were studied using immunocytochemistry. In the nasal mucosa, substance P (SP)- and tyrosine hydroxylase (TH)-like immunoreactive (SPI and THI) fibers seemed to decrease after capsaicin application. Calcitonin gene-related peptide (CGRP)-like immunoreactive (CGRPI) fibers did not show obvious alterations. In the olfactory bulb, SPI and CGRPI fibers were few and the effects of capsaicin on those fibers were difficult to evaluate. THI fibers seemed not to be affected by capsaicin. It is suggested that capsaicin affects not only sensory nerves but that it also impacts on THI sympathetic nerves in the nasal mucosa.
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PMID:Effects of topical capsaicin on autonomic nerves in experimentally-induced nasal hypersensitivity. An immunocytochemical study. 768 Aug 38

We have investigated the ability of compound 48/80 and of histamine H1 and H2 receptor antagonists to inhibit toluene diisocyanate-induced contractions in isolated guinea-pig bronchi. Compound 48/80 (100 micrograms/ml) significantly inhibited toluene diisocyanate-induced contractions. By contrast, the two histamine H1 and H2 receptor antagonists, chlorpheniramine (10 microM) and cimetidine, (10 microM) did not affect toluene diisocyanate-induced contractions, but significantly inhibited contractions induced by exogenously applied histamine (100 microM) and by 48/80. We investigated which mechanisms 48/80 used to inhibit toluene diisocyanate-induced contractions, paying particular attention to the possible involvement of capsaicin-sensitive primary afferents. In vitro capsaicin desensitization (10 microM for 30 min followed by washing) significantly reduced compound 48/80-induced contractions. A capsaicin-resistant component of contraction was also evident. Ruthenium red (3 microM), an inorganic dye which acts as a selective functional antagonist of capsaicin, did not affect 48/80-induced contraction. MEN 10,207 (Tyr5,D-Trp6,8,9,Arg10)-neurokinin A (4-10) (3 microM) a selective antagonist of NK2-tachykinin receptors significantly reduced 48/80-induced contractions. These results show that compound 48/80 inhibits toluene diisocyanate-induced contractions in isolated guinea-pig bronchi. It is likely that two mechanisms are involved in the inhibition: (1) the release of mediators other than histamine by mast cells, (2) an effect of 48/80 on sensory nerves.
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PMID:The effect of compound 48/80 on contractions induced by toluene diisocyanate in isolated guinea-pig bronchus. 768 59

Isocyanates are increasingly being used for manufacturing polyurethane foam, elastomers, adhesives, paints, coatings, insecticides, and many other products. At present, they are regarded as one of the main causes of occupational asthma. The large number of workers who are exposed to these chemicals have a concentration-dependent risk of developing chronic airway disorders, especially bronchial asthma. Different pathophysiologic mechanisms are involved. Immunoglobulin E (IgE)-mediated sensitization and irritative effects have been clearly demonstrated in both exposed subjects and animals. Presumably, neural inflammation due to neuropeptide release of capsaicin-sensitive afferent nerves is crucial. We collected data on 1780 isocyanate workers who had been examined by our groups. Of them 1095 (including subjects from outpatient departments) had work-related symptoms, predominantly of the respiratory tract. Specific IgE antibodies were found in 14% of the 1095 subjects. The methacholine challenge test was shown to be an inadequate predictor of the results of inhalative isocyanate provocation tests in workers and in asthmatic controls. Isocyanate (toluene diisocyanate TDI) air concentrations of 10 ppb (0.07 mg/m3) and 20 ppb (0.14 mg/m3), respectively, did not cause significant bronchial obstruction in the majority of previously unexposed asthmatics with bronchial hyperreactivity. IgG-mediated allergic alveolitis, a rare disease among isocyanate workers, was found in approximately 1% of the symptomatic subjects. Experimental studies exhibit dose-dependent toxic effects and give evidence for tachykinin-mediated bronchial hyperreactivity after exposure to isocyanates. The clinical role of genotoxic effects of isocyanates and their by-products demonstrated here in vitro and in vivo has yet to be clarified.
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PMID:Respiratory and other hazards of isocyanates. 781 92

The aim of the present study was to examine the role of neuropeptides, especially substance P (SP) and neurokinin A (NKA), in toluene diisocyanate (TDI)-induced airway hyperresponsiveness (AHR) to acetylcholine aerosols. Thirty parts per billion of TDI in air administered over 4 hours caused a significant increase in the airway constrictive response to acetylcholine (ACH) aerosols in rabbits (DeltaRI: 245 +/- 30%, p < 0.005) without altering basic values of respiratory, cardiovascular or blood gas parameters. Inhalation of the aerosolized neuropeptides SP and NKA resulted in a similar increase in airway responsiveness (AR) to ACH as exposure to 30 ppb TDI. To determine whether neuropeptides contribute to TDI-induced AHR, we studied their effects after systemic treatment with capsaicin as well as after infusion of specific synthetic antagonists for SP and NK2 (NKA) receptors. CAPS treatment performed on 4 consecutive days as well as antagonists' infusion only moderately (p > 0.05) decreased airway responses to ACH. CAPS application prevented the TDI-induced increase in AR to ACH in all rabbits. The increase in airway resistance to ACH did not significantly change after TDI exposure (98 +/- 22% of the control response before TDI, p > 0.05). Simultaneous infusion of specific synthetic SP and NK2 receptor antagonists also abolished the TDI-induced increase in airway responses to ACH in all animals investigated (p > 0.05). The results of this study demonstrate that neuropeptides, especially the tachykinins SP and NKA, are important mediators in TDI-induced AHR in rabbits.
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PMID:Role of substance P and neurokinin A in toluene diisocyanate-induced increased airway responsiveness in rabbits. 891 32

Dietary Mg-deficiency increases the susceptibility of rat hearts to ischemia-reperfusion (I-R) injury in vitro, and also promotes substance P-associated neurogenic inflammation in vivo. The relationship between Mg-deficiency-induced neurogenic inflammation and the subsequently-enhanced free radical-mediated oxidative and functional injury during I-R was examined using the substance P receptor antagonist, L-703,606. Rats maintained on 3-week Mg-deficient (MgD; <1.8 mmol Mg/kg food) or Mg-sufficient (MgS; 25 mmol Mg/kg) diets were treated during this time with either L-703,606 (1.0 or 3.5 mg/sustained-release pellet, s.c.) or a placebo, prior to isolated perfused I-R. Post-ischemic functional recovery (pressure-volume work), myocardial effluent lactate dehydrogenase (LDH) activity, and lipid hydroperoxides (LOOH) were assessed after 30-min global ischemia. Lipid peroxidation-derived free radical production was monitored by alpha-phenyl-N-t-butylnitrone (PBN) spin trap infusion (2-3 mM final) and toluene-extracted effluents were analyzed by electron spin resonance (ESR) spectroscopy. PBN/alkoxyl adducts (alpha(H) = 1.89-1.93 G, alpha(N) = 13.58-13.63 G) were the dominant ESR signals detected in MgS and MgD I-R hearts; however, MgD hearts exhibited greater total LOOH (2.9 x higher) and alkoxyl adduct production (2.3 x higher), higher tissue LDH release (1.8 x ) and lower functional recovery (51% less) than MgS hearts. MgD rats treated with L-703,606 displayed a dose-dependent improvement in myocardial functional recovery (1.5-2 x higher), and reductions in LDH release (42-59% lower), total LOOH content (36-73% lower) and alkoxyl production (40-65% lower). Interestingly. L-703,606 treatment did not reduce functional impairment or lessen the tissue and oxidative injury experienced by MgS I-R hearts. These findings suggest that L-703,606 reduced oxidative injury and improved functional recovery of MgD I-R hearts by retarding substance P-mediated inflammatory/pro-oxidant events during the in vivo development of Mg-deficiency.
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PMID:Magnesium-deficiency-enhanced post-ischemic myocardial injury is reduced by substance P receptor blockade. 904 25

In this study, the severity and time course of inflammation induced by 4 organic solvents (acetone, cyclohexane, toluene and m-xylene), and the effect of neuropeptides during the inflammation were investigated in the hairless rat abdominal skin. Plasma extravasation used as a parameter of inflammation was measured by Evans blue and 125I-bovine serum albumin (BSA). Total volume of plasma extravasation induced by 4 organic solvents in 240-min exposure was as follows: toluene > m-xylene > cyclohexane > acetone = 0. While hydrophobic solvents (toluene, m-xylene, cyclohexane) induced plasma extravasation, the hydrophilic solvent, acetone, did not induce plasma extravasation. It was suggested that the severity and time course of plasma extravasation depend on chemical characteristics of the organic solvents. In immunohistochemical study, substance P (SP)-immunoreactive nerve fibers (IRNF) and calcitonin gene-related peptide (CGRP)-IRNF were intact during 240-min exposure to acetone. In contrast, cyclohexane, toluene, and m-xylene reduced the number of SP-IRNF and CGRP-IRNF in 10 min exposure and further reduced immunoreactivity. In hairless rats treated with systemic capsaicin, the above plasma extravasation was significantly reduced, along with SP-IRNF and CGRP-IRNF; however, protein gene product 9.5 (PGP 9.5)-IRNF was nearly intact. These results indicated that certain organic solvents induce instance of inflammation that vary widely in terms of their severity and time course, and that these differences are correlated with neuropeptides.
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PMID:Evaluation of organic solvent-induced inflammation modulated by neuropeptides in the abdominal skin of hairless rats. 947 57

To study the density alterations of three peptidergic terminals in nasal mucosa of allergic rhinitis (AR), an exhaustive immunohistochemical sutdy on the changes of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) in nasal mucosa was carried out in a toluene-2, 4-isocyanate (TDI)-induced rat AR model. The densities of all three tachykininergic terminals in nasal mucosa were significantly increased (P < 0.01) in experimental group as compared with control group. Increased staining, thickening of peptidergic terminals as well as enlargement of varicosities were observed. The increased densities of three tachykininergic terminals (SP, NKA and NKB) in nasal mucosa in rat AR model indicates that tachykinins play an important role in the pathogenesis of AR.
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PMID:[Immunohistochemical study on three peptidergic terminals in nasal mucosa in a rat AR model]. 964 48

Rats were sensitized by intranasal application of toluene diisocyanate as a nasal allergy model. By means of the Using chamber technique, rat nasal epithelial short-circuit current (Isc) was measured. Enhanced Isc of the rat nasal mucosa resulted from stimulation of substance P (SP) in a dose-dependent manner that could be inhibited by pretreatment with NK1 receptor antagonist CP-96345, the H1 receptor antagonist pyrilamine, the H2 receptor antagonist ranitidine, and the neurotoxin tetrodotoxin, respectively, to different extents. The results indicate that SP is able to cause ion secretion of the nasal mucosal epithelium, perhaps by activating mast cells to release histamine. These data suggest that mast cells and sensory nerves participate in the regulation of SP-induced ion secretion during nasal allergy.
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PMID:Effect of substance P on the short-circuit current of rat nasal mucosal epithelium. 971 70

Inhalation of irritants, such as toluene diisocyanate (TDI), stimulates substance P (SP) release from peripheral processes of sensory neurons innervating the airways. The purpose of this study was to determine if TDI inhalation affects intraneuronal levels of SP and preprotachykinin (PPT) messenger RNA (mRNA) in the sensory neurons of the trigeminal ganglion (TG) which innervate the nasal epithelium. The nasal cavity of Fisher-344 rats was instilled with rhodamine-labeled latex microspheres. Ten days later, the rats were exposed to 60 ppb of 2,4-2,6-TDI vapor for 2 h. The TG were removed 1, 12, 24, 48, 72, and 96 h after TDI treatment and prepared for SP immunocytochemistry and PPT in situ hybridization. SP nerve fiber density in nasal epithelium was significantly increased 12, 24, and 48 h after TDI exposure. The proportion of microsphere-labeled cell bodies expressing high levels of SP immunoreactivity was decreased at 24 h but was increased above controls at 48 and 72 h. The proportion of microsphere-labeled cell bodies expressing high levels of PPT mRNA was increased above control levels at 24 and 48 h. The percentage of leukocytes observed in nasal lavage fluid was significantly increased 12, 24, 48, and 72 h after inhalation. These studies indicate that SP production in TG neurons projecting to the nasal epithelium is transiently increased after TDI exposure, suggesting that TDI inhalation not only causes SP release but also increased intraneuronal neuropeptide levels. Increased neuronal SP levels may be involved in maintaining neurogenic inflammation or the development of airway hyperresponsiveness.
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PMID:Toluene diisocyanate enhances substance P in sensory neurons innervating the nasal mucosa. 1067 98


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