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)

Many neuropeptides have recently been identified in human and animal airways. These peptides have potent effects on airway caliber, blood vessels, and secretions, raising the possibility that they may be involved in airway diseases such as asthma. Vasoactive intestinal peptide and peptide histidine methionine are potent bronchodilators and may be neurotransmitters of nonadrenergic bronchodilator nerves. In asthma, if these peptides are broken down more rapidly by enzymes from inflammatory cells, this might contribute to exaggerated bronchial responsiveness. Neuropeptides that are found in sensory nerves, such as substance P, neurokinin A, and calcitonin gene-related peptide, have inflammatory effects and might also contribute to the pathology of asthma if released from sensory nerve endings by an axon reflex. These findings may have important therapeutic implications for the future.
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PMID:Neuropeptides and asthma. 170 52

We compared the cutaneous reaction to intradermal injection of substance P, gastrin and histamine in asymptomatic atopic subjects with a history of hay fever and/or asthma versus non-atopic healthy volunteers. We also studied in these two groups the basophilic histamine release induced by substance P and gastrin with that obtained with anti-human IgE and Con A. Intradermal injection of substance P (3-300 pM) and gastrin (3-30 pM) caused a wheal and flare reaction which was comparable in both groups of subjects. Substance P 10(-4)M caused a mean basophilic histamine release of about 15% in atopic and non-atopic subjects. Gastrin was not effective in this model. Anti-IgE and Con A-induced histamine release was significantly higher in atopic than in non-atopic volunteers.
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PMID:Cutaneous and basophilic sensitivity to substance P and gastrin in non-atopic versus atopic subjects. 170 11

1. Sensory neuropeptides such as substance P may be implicated in the pathophysiology of asthma. 2. It has been proposed that nedocromil sodium may inhibit the effects of neuropeptides. 3. In this study, using an isolated innervated preparation of rabbit trachea, substance P, 10(-6) M, potentiated contractions induced by parasympathetic stimulation. The effect of substance P at the preganglionic site (307 +/- 38% of control, n = 5), was similar to that at the postganglionic site (307 +/- 61% of control, n = 5). 4. Nedocromil sodium, 10(-7) M, significantly inhibited the substance P-induced potentiation preganglionically (199 +/- 44%, n = 4, P less than 0.05) but not postganglionically (356 +/- 118%, n = 4). 5. These results suggest that nedocromil sodium may modify neuropeptide action selectively at a preganglionic site and that this may contribute to its therapeutic efficacy.
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PMID:Nedocromil sodium inhibits substance P-induced potentiation of cholinergic neural responses in the isolated innervated rabbit trachea. 171 86

1. Opioids have been shown to inhibit substance P (SP) release from primary afferent neurones (PAN). In addition, opioid receptors have been identified on PAN of the vagus nerves. Sodium cromoglycate (SCG) decreases the excitability of C-fibres in the lung of the dog in vivo. We have utilised a multi-superfusion system to investigate the effect of opioids and SCG on the release of SP from the rat trachea in vitro. 2. Pretreatment of newborn rats with capsaicin (50 mg kg-1 s.c. at day 1 and 2 of life) resulted in a 93.2 +/- 6.3% reduction in tracheal substance P-like immunoreactivity (SP-LI) content when determined by radioimmunoassay in the adult. 3. Exposure to isotonically elevated potassium concentrations (37-90 mM), capsaicin (100 nM-10 microM), and bradykinin (BK; 10nm-1 microM) but not des-Arg9-BK (1 microM) stimulated SP-LI release by a calcium-dependent mechanism. 4. SCG (1 microM and 100 microM) did not affect spontaneous, potassium (60 mM)- or BK (1 microM)-stimulated SP-LI release. 5. Morphine (0.1-100 microM) caused dose-related inhibition of potassium (60 mM)-stimulated SP-LI release with the greatest inhibition of 60.4 +/- 13.7% at 100 microM. The effect of morphine was not mimicked by the kappa-opioid receptor agonist, U50,488H (10 microM) or the delta-opioid receptor agonist, Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE). 6. The effect of morphine was totally abolished by prior and concomitant exposure to naloxone (100 nM) which had no effect on control release values. 7. We conclude that opioid receptors, predominantly of the MM-opioid receptor subtype, inhibit SP-LI release from PAN in the rat trachea and suggest that centrally inactive MM-opioid receptor agonists may have therapeutic potential in the treatment of asthma.
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PMID:Morphine, but not sodium cromoglycate, modulates the release of substance P from capsaicin-sensitive neurones in the rat trachea in vitro. 171 4

1. The role of gamma-aminobutyric acid (GABA) as an inhibitory transmitter in the central nervous system is well documented. Recently, GABAA and GABAB receptors have been identified in the peripheral nervous system, notably on primary afferent neurones (PAN). We have utilised a multi-superfusion system to investigate the effect of selective GABA receptor agonists and antagonists on the release of substance P (SP) from the rat trachea in vitro. 2. GABA (1-100 microM) did not affect spontaneous release of SP-like immunoreactivity (LI) but caused dose-related inhibition of calcium-dependent potassium (60 mM)-stimulated SP-LI release. The greatest inhibition of 77.7 +/- 18.8% was observed at 100 microM. 3. The inhibitory effect of GABA was mimicked by the GABAB receptor agonist, (+/-)-baclofen (1-100 microM), but not the GABAA receptor agonist, 3-amino-1-propane-sulphonic acid (3-APS, 1-100 microM). Baclofen (100 microM) had no effect on SP-LI release stimulated by capsaicin (1 microM). 4. The inhibitory effect of baclofen (30 microM) was significantly reduced by prior and concomitant exposure to the GABAB receptor antagonist, phacolofen (100 microM) but not the GABAA receptor antagonist, bicuculline (10 microM). Neither antagonist, alone, affected spontaneous or potassium-stimulated SP-LI release. 5. We conclude that activation of pre-synaptic GABAB receptors on the peripheral termini of PANs in the rat trachea inhibits SP-LI release and suggest that GABAB receptor agonists may be of value in the therapeutic treatment of asthma.
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PMID:GABAB receptor modulation of the release of substance P from capsaicin-sensitive neurones in the rat trachea in vitro. 171 5

Substance P has been localized to nerves supplying smooth muscle, blood vessels and glands in the human lung and may play a major role in the pathophysiology of asthma. We performed a morphological study, using the avidin biotin peroxidase immunostaining technique, to examine sections of airway wall from subjects with and without asthma for the presence of substance P immunoreactive nerve fibres. Airways of 200 microns-12 mm were obtained from autopsy, lobectomy and bronchoscopy. Quantitative morphological analysis was performed on 3 mm diameter airways from three asthmatic and three nonasthmatic subjects collected at autopsy, and on biopsies of 10 mm diameter airways from eight asthmatic and thirteen nonasthematic subjects. There was an increase in both the number and the length of substance P immunoreactive nerve fibres, in airways from subjects with asthma when compared with airways from subjects without asthma. Fibres were found in the lamina propria and surrounding vessels and glands. The fibres were commonly seen as bundles rather than as single fibres. There was no difference in the number of substance P nerves between normal subjects and subjects with chronic airflow limitation (CAL). The difference in the number, length and morphological characteristics of the substance P immunoreactive nerves between asthmatic and nonasthmatic subjects were striking.
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PMID:Substance P immunoreactive nerves in airways from asthmatics and nonasthmatics. 171 17

To investigate neural events within the airways in asthma, endobronchial biopsies were obtained by fibre-optic bronchoscopy from 8 atopic asthmatic subjects and 8 non-atopic healthy controls. The biopsies were immediately fixed on sampling and subsequently analysed for nerves using specific indirect immunofluorescence with antisera to the neural marker PGP 9.5 and to the neuropeptides vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). Nerves were present in all the biopsies from both subject groups, with no significant difference between the asthmatic and non-asthmatics. VIP-immunoreactive nerves were equally present in both subject groups, being localized to smooth muscle and glandular sites. No immunoreactive nerves to SP or CGRP could be identified in any biopsy at any location. These in vivo findings do not identify an anatomical neuronal imbalance in asthma.
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PMID:Mucosal nerves in endobronchial biopsies in asthma and non-asthma. 171 95

It was shown in two different provocation models (nasal and bronchial provocation) that substance P (SP) may play an important role in the neurogenic inflammatory response in upper and lower airway disease. (1) Pretreatment with SP augments the antigen challenge response of the nasal mucosa. (2) The baseline bronchoalveolar lavage (BAL) concentrations of SP are elevated 8-fold in allergies (pollen asthma) as compared with normals, even outside of season. (3) The SP concentration in BAL increases significantly (p less than 0.05) after bronchial allergen provocation. These findings support a previous hypothesis of an abnormally elevated activity of nonadrenergic-noncholinergic excitatory nerves and are in accordance with the results of a decreased activity of neutral endopeptidase exaggerating neurogenic inflammatory responses in the airways, including bronchomotor tone hyperresponsiveness.
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PMID:The possible role of substance P in the allergic reaction, based on two different provocation models. 171 96

Human blood polymorphonuclear neutrophils (PMN) are thought to be involved in the pathogenesis of asthma through their recruitment into the bronchoalveolar lumen and the lung by local release of chemotactic factors. Therefore chemotactic activities of several mediators (PAF, histamine and three neuropeptides substance P, VIP and a somatostatin analog) were compared on blood PMN from both healthy subjects (HS) and asthmatic patients (AP). The maximal response to PAF was significantly different (P less than 0.05) with cells from both groups. Moreover activity for the HS peaked at 10(-6) M, whereas the AP showed peak chemotactic activity at 10(-8) M. Histamine had no chemoattractant effect on PMN. Substance P did not induce PMN locomotion, whereas VIP induced a chemotactic response in a dose-dependent manner, particularly with cells from HS as compared to those from AP. BIM 23014 (a somatostatin analog) exhibited chemotactic activity which was also more pronounced with PMN from HS as compared to those from AP. Our findings showed that blood PMN could be involved in asthma through their heightened locomotor reactions to mediators which are known to be released locally by activated cells in bronchoalveolar lumen.
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PMID:Neutrophil chemotactic activity of PAF, histamine and neuromediators in bronchial asthma. 172 27

1. In addition to the classical cholinergic bronchoconstrictor and adrenergic bronchodilator neural mechanisms, there is a large volume of evidence to suggest the existence of neural pathways within the airways of a variety of species which are neither adrenergic nor cholinergic, the non-adrenergic, non-cholinergic (NANC) mechanisms. With respect to airway smooth muscle tone, NANC neural responses may induce either contraction (excitatory, e-NANC) or relaxation (inhibitory, i-NANC). Early investigations of NANC mechanisms in both human and other animal airways suggested a role for neuropeptides as the putative neurotransmitters. 2. Excitatory NANC (e-NANC) bronchoconstrictor responses are believed to be mediated by the release of sensory neuropeptides from a subpopulation of non-myelinated C-fibre primary afferent neurones in the airways. e-NANC nerves, which release tachykinins such as substance P (SP), neurokinin A (NKA) and the peptide calcitonin gene-related peptide (CGRP, produced as a result of alternative splicing of the calcitonin gene) are selectively degenerated by the nerve toxin capsaicin (an extract from hot peppers), with the subsequent abolition of the e-NANC responses. Tachykinin receptors have been detected by radio-ligand receptor binding studies and visualized by autoradiographic mapping, and exogenous addition of these peptides elicits a bronchoconstrictor response in both human and other animal airways. In addition to these effects on airway smooth muscle tone, tachykinins produce an increase in microvascular permeability (and associated oedema formation), mucus hypersecretion and cause an exaggerated cholinergic bronchoconstrictor response. Thus, tachykinins may play a role in the inflammatory process and contribute to the neurogenic inflammation as seen in asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Non-adrenergic, non-cholinergic neural control of the airways. 176 11


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