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)

1. The effects of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) were evaluated on superoxide anion (O2-.) production by guinea-pig alveolar macrophages (AM). 2. SP dose-dependently (ED50 = 0.7 nM) evoked O2-. production from guinea-pig AM; the N-terminal heptapeptide, SP(1-7), was ineffective. In the presence of thiorphan (10(-5) M), an enkephalinase inhibitor, the stimulating effects of SP were not significantly modified. NKA and NKB were both able to induce O2-. production from guinea-pig AM, ED50 values being 0.1 and 1.3 nM, respectively. Therefore, the rank order of activity of natural tachykinins was NKA greater than SP greater than NKB. Tachykinin-evoked effects were quantitatively similar to those elicited by the autacoid mediator PAF-acether and less than those induced by the synthetic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP). 3. The NK2 receptor agonist [beta-Ala8]-NKA (4-10) dose-dependently evoked O2-. production from guinea-pig AM; the NK1 receptor agonist [Pro9]-SP sulphone acted only at high concentrations, while the NK3 receptor agonist [Me,Phe7]-NKB was ineffective. 4. These findings indicate that guinea-pig AM possess NK2 and possibly some NK1 tachykinin receptors and further suggest tachykinin involvement in lung pathophysiology.
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PMID:Tachykinins activate guinea-pig alveolar macrophages: involvement of NK2 and NK1 receptors. 169 94

A large amount of mucus and mucoid impaction are observed in the autopsied lungs of bronchial asthmatics. It is possible that mucus hypersecretion and accumulation of intrabronchial mucus result in bronchial obstruction and structural bronchial hyperresponsiveness. Bronchial gland plays a main role in human airway secretion. We describe here some results using isolated gland preparation which enable us to examine airway mucus secretion in a well-defined condition. Chemical mediators released from mast cells augment the secretory responses induced by cholinergic nerve stimulation through accelerated acetylcholine release in the nerve terminals. PAF produces an increase in mucus glycoprotein secretion in the presence of platelets mainly through the thromboxane release from platelets. Substance P which is released by an axon reflex in response to various stimuli and inflammations in the airways, also produced an increase in mucus secretion. Epithelial cells release an inhibitory factor to mucus glycoprotein secretion from bronchial glands. Epithelial cell damages due to inflammation in the airways may induced a reduction of the inhibitory factor release in bronchial asthmatics, resulting in mucus hypersecretion.
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PMID:[Airway hyperresponsiveness and mucus secretion]. 170 51

Using a computer-assisted image analyser, an immunohistochemical quantification method of substance P-like immunoreactivity (SPLI) in laminae I + II of spinal dorsal horn was established and applied to 13 patients with multiple system atrophy (MSA) with no disturbance of pain sensation, including olivo-ponto-cerebellar atrophy and striatonigral degeneration, and 13 neurologically normal controls. To investigate whether alteration of SPLI is related to an autonomic disorder, myelinated fibre counts of the fourth thoracic ventral roots were performed. Eleven of 13 MSA patients showed a significant decrease in small and large myelinated fibres, and were diagnosed with definite Shy-Drager syndrome (SDS), with the exception of two who had no apparent history of autonomic dysfunction. SPLIs in laminae I + II in 10 of these 11 patients, when adjusted for age, were significantly decreased at both levels of the fourth thoracic and third lumbar spinal segments. The results suggest the disorder of SP-containing synapses of primary afferent neurons and/or those of interneurons in SDS.
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PMID:Immunohistochemical quantification of substance P in spinal dorsal horns of patients with multiple system atrophy. 171 85

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

Tracheas from control rats or rats sensitized to egg albumin (EA) were studied in vitro in Ussing chambers, and changes in short-circuit current (Isc) induced by the addition of antigen or agonists on the mucosal (luminal) side were recorded. Addition of EA (100 micrograms/ml) to tracheas from sensitized but not from control rats caused a slow increase of Isc beginning after 15 to 30 s and maximal at 3 to 4 min. This response was inhibited in the presence of doxantrazole, a mucosal mast-cell-stabilizing agent, but not by sodium cromoglycate. A separate group of rats was treated neonatally with capsaicin to deplete peptide neurotransmitters. Responses to EA were significantly lower in capsaicin-treated, sensitized rats than in untreated, sensitized control littermates. No difference was seen in the level of serum EA-specific IgE in these two groups. In tracheas from untreated rats, addition of substance P, capsaicin, platelet-activating factor, and acetylcholine caused an immediate and marked increase in Isc. Responses to substance P and acetylcholine were unaffected by capsaicin treatment. However, responses to capsaicin itself and also to PAF were reduced. These data indicate that changes of net ion transport across the airway epithelium are early phenomena of local hypersensitivity reactions, and that neurotransmitters such as substance P may play an important role in the control of these phenomena.
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PMID:Ion transport in rat tracheal epithelium in vitro. Role of capsaicin-sensitive nerves in allergic reactions. 196 24

1. An epithelium-derived inhibitory factor (EpDIF) released by guinea-pig tracheal epithelium was evaluated in a co-axial bioassay system consisting of an epithelium-intact guinea-pig tracheal tube surrounding endothelium-denuded rat aortic strip. 2. Histamine and several muscarinic agonists induced concentration-dependent relaxation of phenylephrine-contracted rat aorta via the release of EpDIF. However, several other agonists did not induce the release of EpDIF from guinea-pig trachea. These included the nicotinic cholinoceptor agonists nicotine (25 microM), 1,1-dimethyl-4-phenylpiperazinium (DMPP) (25 microM), calcium ionophore A23187 (0.5 microM), bradykinin (0.05-0.5 microM), substance P (5 microM), platelet activating factor (PAF, 1-100 nM), the leukotrienes (LT) LTC4, LTD4 and LTE4 (0.1-10 nM) as well as hyperosmotic stimuli. 3. Prostaglandin E2 (PGE2) induced concentration-dependent contraction of endothelium-denuded rat aortic preparations, indicating that this prostanoid could not be EpDIF. Furthermore, relaxation to histamine and methacholine, mediated via EpDIF, was not significantly altered in the presence of phenidone (50 microM) the cyclo-oxygenase/lipoxygenase inhibitor with radical scavenging properties or the cytochrome P-450 inhibitors metyrapone (1 mM) and SKF 525A (25 microM). This suggests that EpDIF is neither a prostanoid nor a cytochrome P-450 metabolite of arachidonic acid. 4. The soluble guanylate cyclase inhibitor, methylene blue (50 microM), caused small but significant increases in the potencies of both histamine and methacholine in co-axial assemblies, indicating that EpDIF did not activate this enzyme and therefore was not NO or a related substance. The beta-adrenoceptor antagonist, (-)-propranolol (1 microM), and the PAF-receptor antagonist, WEB 2086 (50 microM), also failed to alter significantly EpDIF-modulated relaxations. These data suggest that EpDIF is neither a stimulant of fiadrenoceptors nor of PAF receptors. 5. The present study provides some evidence that this vascular smooth muscle-sensitive EpDIF may not be related to the putative EpDIF previously hypothesized to modulate directly spasmogen-induced airway smooth muscle tone.
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PMID:Pharmacological evaluation of a guinea-pig tracheal epithelium-derived inhibitory factor (EpDIF). 239 Jun 83

When rats were pretreated by intraplantar or i.v. injection of various inflammatory mediators, the vasopressor effect of i.a. norepinephrine in the subsequently isolated perfused hindlegs of the rats was found to be partly depressed. This vasodepression could also be detected if mediators were directly co-perfused in the isolated hindlegs. The vasodepressor effect was strongest following histamine pretreatment and co-perfusion, respectively, whereas endotoxin 0111:B4, PAF-acether, PGE1, and LTD4 were less effective. Only weak or no vasodepression could be induced by bradykinin, serotonin, lysolecithin, and substance P (1-11). The significance of the results is discussed with respect to anaphylactic disorders.
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PMID:Vasodepression ex vivo after administration of inflammatory mediators in vivo in the rat. 247 18

In the anterior segment of the eye, phosphoinositides of the iris-ciliary body are the major source of AA for PG biosynthesis. In the past several years, we have demonstrated that these phospholipids are highly enriched in AA and have an extremely high metabolic turnover. We have also discovered that their metabolism by phospholipase C, which leads to the formation of IP3 and DG and the liberation of AA, is controlled by the following Ca2+-mobilizing receptors: alpha 1-adrenergic, M3- or M4-muscarinic cholinergic, substance P, and PGs. The release of IP3, DG, and AA in the iris was also demonstrated under in vivo conditions. Furthermore, it was demonstrated that this release is associated with denervation supersensitivity and subsensitivity of the iris. Two pathways have been demonstrated in the iris through which AA can be released directly from phosphoinositides: (a) Phosphoinositides can be hydrolyzed by phospholipase C, followed by hydrolysis of DG via lipases to liberate AA, and (b) AA can be released directly from phosphoinositides via phospholipase A2. Although the evidence for a link between Ca2+-mobilizing receptors and phospholipase C, via G proteins, has been well established, the precise link between these receptors and phospholipase A2 is still unclear. Our studies indicated that PGs may be involved in regulation of contraction and relaxation of the smooth muscles of the iris by increasing IP3 accumulation and consequently Ca2+ mobilization and by elevating the level of cAMP which in turn facilitates muscle relaxation. In addition, evidence of a link between the two pathways through the Ca2+ signaling system has been suggested. In the iris, PAF was found to liberate AA from phosphoinositides through the phospholipase A2, but not the phospholipase C pathway, thus emphasizing the role of this pathway in PG synthesis in the eye. These findings demonstrate that AA release and, consequently, PG synthesis in the iris of the eye are exquisitely regulated. In some species, such as bovine, cat and dog, PGs were found to act as full Ca2+ mobilizing agonists. It is possible that PGs function to maintain muscle tone in the resting iris smooth muscle cells, in addition to their involvement in various Ca2+-dependent processes. Our studies indicate that PGs may be involved in regulation of contraction and relaxation of the smooth muscles of the iris by increasing IP3 accumulation and consequently Ca2+ mobilization and by elevating the level of cAMP which in turn facilitates muscle relaxation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of arachidonate release, prostaglandin synthesis, and sphincter constriction in the mammalian iris-ciliary body. 255 69

Recent studies have suggested that inflammation may play an important role in the characteristic bronchial hyperresponsiveness and symptoms of chronic asthma. The mechanisms by which inflammatory cells, mediators, and nerves interact to produce the features of asthma are still uncertain, however. Although mast cells play an important role in the immediate response to allergen (and probably exercise), pharmacologic evidence argues against a critical role in the late response or bronchial hyperresponsiveness in which other cells, such as macrophages and eosinophils, may play a more important role. Many mediators have been implicated in asthma, but only PAF causes a prolonged increase in bronchial responsiveness. PAF attracts eosinophils into tissues and potently activates these cells, which may lead to epithelial damage, a key feature of asthmatic airways. PAF is also a potent inducer of microvascular leakage in airways, which may result in submucosal edema and plasma exudation into the airway lumen in the future. PAF antagonists will reveal whether PAF plays an important role in the eosinophilic inflammation of asthma. Neural mechanisms may also make an important contribution. Inflammatory mediators may influence neurotransmitter release from airway nerves, and neurotransmitters may be proinflammatory. Neural control is complex and cholinergic, adrenergic, and NANC mechanisms may contribute to bronchial hyperresponsiveness. Many neuropeptides, which may be the transmitters of NANC nerves, have been identified in airways. Neuropeptides in airway sensory nerves, such as substance P, have potent proinflammatory effects and, if these are released by an axon reflex, may amplify the inflammatory response in asthma. Since asthma may be chronic eosinophilic bronchitis, it is logical that the primary treatment should involve drugs that suppress this inflammatory response. At present, corticosteroids appear to be the most effective therapy; they have potent effects against eosinophils and macrophages (but not on mast cells) and reduce bronchial hyperresponsiveness and symptoms. By contrast, bronchodilators, such as beta-agonists, although they reduce symptoms, do not reduce the chronic inflammatory response or bronchial hyperresponsiveness and may mask the underlying inflammation. New therapies should be directed toward controlling eosinophil infiltration and activation in airways.
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PMID:New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma. 265 43

The aim of this review is that to examine some among the most important mediators involved in the onset of autacoid-mediated allergic and non-allergic symptomatology. Autacoids, such as histamine and arachidonic acid derivatives (leukotrienes and prostaglandins), mediators derived from cell membrane, such as PAF-acether and other cell-derived mediators, such as PF4, are described. Special importance is given to the respective pharmacological actions and to the mechanisms by which these actions are performed (receptors, antagonisms, synergism) from whose complexity systemic reactions might ensue. Furthermore, a part of this study is dedicated to the complex interactions among biochemical systems of the body such as Kinins, Coagulation, Fibrinolysis and Enzymatic Activity Mediators that can interfere with these interactions and support some pathologies. Besides, a chapter is devoted to Neurogenic Inflammation and therefore to Substance P and other neuropeptides.
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PMID:Autacoids and some mediators in allergic and non allergic forms. 287 78


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