Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of nerve fibers and cell bodies reactive for the peptides enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide were studied in biopsies of external muscle taken from the gastric body and antrum of 17 patients undergoing surgery for gastroesophageal reflux, and in regions of healthy stomach resected as part of gastric cancer operations. The results were correlated with preoperative measurements of liquid and solid emptying from the stomach in the patients with gastro-esophageal reflux. In three cases, no delay was detected in either liquid or solid emptying, and the distribution of peptide immunoreactive fibers in the external muscle was similar to that of healthy muscle. In 14 cases, the emptying of either liquids or solids or both was delayed, and in eight of these clearcut changes in the distribution of peptide-immunoreactive fibers occurred. In six cases, the number of enkephalin-immunoreactive fibers was fewer than normal in the biopsy from the gastric body (in one of these samples the number of substance P-immunoreactive fibers was also reduced). In another cae, the number of substance P-immunoreactive fibers in the antrum was reduced, and in another the number of vasoactive intestinal peptide and neuropeptide Y-immunoreactive fibers in the antral biopsy was reduced. It is concluded that in patients with gastroesophageal reflux who have delayed gastric emptying, a proportion demonstrate abnormalities of the peptide-immunoreactive fibers that innervate the gastric external muscle.
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PMID:Distribution of peptide-containing nerve fibers in the gastric musculature of patients undergoing surgery for gastroesophageal reflux. 138 Feb 32

Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polypeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neuropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.
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PMID:Regulatory peptides in the lower esophageal sphincter of man. 258 Dec 86

Repeated oesophageal acidification is a definitive feature of gastro-oesophageal reflux disease, which in turn is caused by relaxation of the lower oesophageal sphincter (LOS). This study in anaesthetised ferrets investigates the reflex pathways involved in effects of oesophageal acidification on motor function of the LOS, with particular focus on the role of tachykinins. LOS pressure was monitored with a perfused micromanometric sleeve assembly. Oesophageal acidification reduced LOS pressure by 48 +/- 5% until washout with saline. This reduction became larger with repeated tests, and was unaffected in amplitude by acute bilateral vagotomy, although the response became slower in onset. Intra-oesophageal capsaicin (0.5% solution) caused a 68 +/- 17% decrease in LOS pressure which remained unchanged with repeated tests. The NK-1 receptor antagonist CP96,345 (1-5 mg/kg intravenous (i.v.) blocked the post-vagotomy LOS responses to both intra-luminal acid and capsaicin. Close intra-arterial (i.a.) injections of capsaicin (1-100 micrograms) gut induced LOS relaxation which was neither vagally nor NK-1 receptor-mediated. Substance P or the selective NK-1 receptor agonist [Sar9, Met(O2)11] substance P (25-500 ng close i.a.) caused a biphasic LOS response, consisting of initial brief contraction followed by prolonged, dose-dependent relaxation. Tetrodotoxin (10 micrograms/kg close i.a.) changed the biphasic response to substance P to excitation only. The neurokinin-1 (NK-1) receptor antagonist CP96,345 (0.3-10 mg/kg i.v.) dose-dependently reduced the inhibitory response to substance P. The excitatory phase of the response to substance P was larger and prolonged after guanethidine (5 mg/kg, i.v.), or propranolol (1 mg/kg, i.v.). L-NAME (100 mg/kg i.v.) reduced the inhibitory phase. The selective NK-2 receptor agonist [beta-Ala8] neurokinin A(4-10) caused LOS excitation only. These data indicate that intra-oesophageal acid causes substance P release from extrinsic afferent nerve endings which activates local inhibitory pathways to the LOS via NK-1 receptors.
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PMID:Lower oesophageal sphincter responses to noxious oesophageal chemical stimuli in the ferret: involvement of tachykinin receptors. 940 24

Many different conditions and diseases cause cough. The commonest acute causes are pollution, including cigarette smoke, and upper respiratory tract infection. The commonest chronic causes are postnasal drip, asthma, chronic bronchitis and gastro-oesophageal reflux. Epidemiological studies give widely different patterns of incidence. The different conditions that cause cough have in common the fact that the cough is mediated via the vagus nerves, with sensory receptors in and under the epithelium from the larynx down to the smaller bronchi. These receptors are polymodal, responding to a large variety of stimuli, including mechanical and chemical irritants, inflammatory mediators, intraluminal material and large volume changes of the lungs. With irritation and inflammation, C fibre receptors release neurokinins such as substance P, which in turn stimulate cough receptors. The central nervous pathways for the cough reflex are poorly understood. They can be activated or inhibited voluntarily. Studies on the pharmacology of the central nervous pathways of coughing are opening up new therapeutic possibilities. Other new therapies include drugs acting on the sensory receptors for cough, thereby avoiding adverse central nervous effects.
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PMID:Advances in understanding and treatment of cough. 1044 86

Gastroesophageal reflux (GER) is a potential trigger of asthma. GER symptoms are more prevalent in asthma patients compared with control populations, with a prevalence of approximately 75%. GER symptoms are associated with respiratory symptoms and inhaler use. GER may also occur without esophageal symptoms. Abnormal esophageal acid contact times are also more prevalent in patients with asthma compared with control populations, with a prevalence of 80%. Pathophysiologic mechanisms of esophageal acid-induced bronchoconstriction include a vagally mediated reflex, heightened bronchial reactivity, and microaspiration. Esophageal acid may increase minute ventilation without evidence of bronchoconstriction. Esophageal acid is associated with the release of substance P in the bronchial mucosa, resulting in airway edema. Medical antireflux therapy with proton pump inhibitors results in asthma symptom improvement in approximately 70% of patients, similar to surgical results. Predictors of asthma response include the presence of regurgitation, proximal acid reflux, esophagitis healing with therapy, reflux-associated respiratory symptoms, or nocturnal asthma. Management of GER in adult patients with asthma should include a 3-month trial of high-dose proton pump inhibitor while monitoring asthma outcome. GER should be considered as a potential asthma trigger in all patients.
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PMID:Gastroesophageal reflux and asthma: insight into the association. 1045 38

Gastroesophageal reflux (GERD) may trigger asthma. Approximately 77% of asthmatic people experience reflux symptoms, although GERD may be clinically silent in some. Esophagitis is found in 43% of asthmatic people, and 82% have abnormal esophageal acid contact times on esophageal pH testing. Clearly, GERD is prevalent in asthmatic people. Pathophysiologic mechanisms of acid-induced bronchoconstriction include a vagally mediated reflex and microaspiration. Whether these airway responses are clinically significant is the subject of some debate. Interestingly, peak expiratory flow rates and specific airway resistance alterations persist despite esophageal acid clearance. Preliminary evidence shows that substance P, an inflammatory mediator that causes airway edema, is released with esophageal acid. Although therapeutic studies are limited by their small population sizes and study design, up to 70% of asthmatic people have asthma improvement with antireflux therapy. Possible predictors of asthma response include patients with symptomatic esophageal regurgitation; abnormal proximal esophageal acid exposure; and, in surgical studies, those with normal esophageal motility and asthma response with medical therapy. Future research will further define the association between asthma and gastroesophageal reflux.
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PMID:Gastroesophageal reflux disorders and asthma. 1081 52

In asthma patients, microaspiration of acid into the lower airways (ie, airway acidification) causes such respiratory responses as cough and bronchoconstriction. The mechanism of bronchoconstriction induced by airway acidification is unknown, although evidence is emerging that increasing proton concentrations in airway tissues can activate a subpopulation of primary sensory neurons, so-called capsaicin-sensitive primary sensory neurons, that contain such neuropeptides as the tachykinins substance P (SP) and neurokinin A (NKA). Protons activate a capsaicin-operated channel/receptor, located in the afferents of capsaicin-sensitive neurons, with the subsequent opening of ion channels that are permeable to sodium, potassium, and calcium ions. This event initiates a propagated action potential that antidromically depolarizes collateral fibers and triggers neuropeptide release from nerve fiber varicosities. The tachykinins SP and NKA, released from terminals of primary sensory neurons in peripheral tissues, cause all the major signs of inflammation (neurogenic inflammation) by means of activation of NK(1) and NK(2) receptors. Exposure of the airways to acidic solutions stimulates sensory nerve endings of capsaicin-sensitive sensory neurons and causes different airway responses, including bronchoconstriction. Recently, the NK(2), and to a lesser extent the NK(1), receptors have been shown to be involved with citric acid-induced bronchoconstriction in the guinea pig, which is in part mediated by endogenously released bradykinin. Tachykinins and bradykinin, released by airway acidification, could also modulate citric acid-induced bronchoconstriction by their ability to subsequently release the epithelially derived bronchoprotective nitric oxide (NO). Further study with selective tachykinin NK(1) and NK(2) agonists demonstrated that only the septide-insensitive tachykinin NK(1) receptor releases NO. Thus, bronchoconstriction induced by citric acid inhalation in the guinea pig, mainly caused by the tachykinin NK(2) receptor, is counteracted by bronchoprotective NO after activation of bradykinin B(2) and tachykinin NK(1) receptors in airway epithelium. If a similar mechanism is involved in the pathogenesis of bronchial asthma associated with gastroesophageal reflux in the respiratory tract, new therapeutic strategies should be investigated.
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PMID:Mechanisms of citric acid-induced bronchoconstriction. 1174 19

Gastro-oesophageal reflux is a common clinical disorder associated with a variety of respiratory symptoms, including chronic cough and exacerbation of asthma. In this study, the potential role of acid-induced tachykinin release was examined in guinea pigs and rabbits, by examining the effects of the tachykinin NK1 and NK3 receptors antagonists (SR 140333 and SR 142801, respectively) (1-10 mg x kg(-1)) on plasma protein extravasation induced in airways by hydrochloric acid (HCl) infusion in the oesophagus. Guinea pigs were anaesthetised with urethane, while rabbits were subject to neuroleptoanalgesia with hypnorm. Airway vascular leakage was evaluated by measuring extravasation of Evans blue dye. All animals were pretreated with atropine (1 mg x kg(-1) i.p.), propranolol (1 mg x kg(-1) i.p.), phosphoramidon (2.5 mg x kg(-1) i.v.) and saline or tachykinin receptor antagonists (1-10 mg x kg(-1) i.p.). Infusion of 1 N HCl into the oesophagus led to a three- and five-fold increase in plasma extravasation in the main bronchi and trachea, respectively. This increase was largely prevented by the tachykinin NK1 and NK3 receptor antagonists SR 140333 and SR 142801 (1-10 mg x kg(-1)). These results suggest that protein extravasation in the airways, as induced by intraoesophageal HCl infusion, is mainly dependent on the release of tachykinins, and that both NK1 and NK3 tachykinin receptors are involved. The results suggest that HCl-induced sensory nerve stimulation may act in the periphery on intermediate neurons and/or ganglia where NK3 receptors have been shown to play an important role.
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PMID:Tachykinins and airway microvascular leakage induced by HCl intra-oesophageal instillation. 1221 54

Vagal afferents are extensively distributed in the digestive tract from the oesophagus to the colon. They are involved in the reflex control of normal gastrointestinal (GI) tract function (e.g. secretion and motility) as well as reflexes more characteristic of diseases such as functional dyspepsia and gastroesophageal reflux disease (e.g. vomiting, disordered lower esophageal sphincter relaxation and gastric accommodation). They are also implicated in signalling non-painful sensations (e.g. nausea and early satiety) associated with disease. A variety of receptors has been identified on vagal afferents, which can either enhance (e.g. 5-HT3, CCK1, VR1 and NK1 receptors) or reduce (e.g. ghrelin, leptin, k-opioid and GABAB receptors) activity, offering a range of potential therapeutic targets. Commonly used laboratory species (e.g. rat and mouse) lack an emetic reflex, and the implications of this for models of upper GI disorders have been explored in the light of expanding knowledge of the neuropharmacology of the emetic reflex implicating glutamate, prostanoids, cannabinoids and substance P. Additional pathophysiological roles for vagal afferents (e.g. in thermoregulation, arousal and fatigue) are being investigated, raising the intriguing possibility of the vagus as a target in non-GI disorders.
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PMID:Abdominal vagal afferent neurones: an important target for the treatment of gastrointestinal dysfunction. 1248 26

Airway hyperresponsiveness is among the defining phenomena in asthma. In this article, 3 mechanisms are reviewed to explain how gastroesophageal reflux (GER) may influence airway hyperresponsiveness. First, microaspiration may cause not only direct tissue injury, but may also trigger vagal reflexes. Second, acid infusion of the esophagus in a dog model and in humans has been shown to result in vagally mediated reflexes leading to bronchoconstriction. These reflexes have been studied using immunohistochemical techniques. Third, neuroinflammatory reflexes have been found to play a role in airway responses through the release of tachykinins, including substance P and neurokinin A. Combined, these 3 mechanisms may lead to an increase in vagal efferent impulses that can cause or augment airway hyperresponsiveness. Studies indicate that there is an increase in airway responsiveness in asthma patients who have documented GER. Further, based on the reported number of reflux episodes occurring during 24-hour pH monitoring, airway hyperresponsiveness to methacholine challenge tends to increase as GER worsens.
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PMID:Possible mechanisms of influence of esophageal acid on airway hyperresponsiveness. 1292 76


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