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 distribution of peptide-containing nerve fibers in the pharyngeal region of rabbits was studied by immunocytochemistry. Neuropeptide Y (NPY)-containing fibers were numerous around blood vessels and moderate in number among bundles of striated muscle fibers. A few NPY-containing fibers were seen around seromucous glands and beneath the epithelium. Nerve fibers containing vasoactive intestinal peptide (VIP) were numerous around seromucous glands and moderate in number around blood vessels, bundles of muscle, and in the subepithelial layer. A few nerve fibers containing substance P (SP) were seen around blood vessels, seromucous glands, among bundles of muscle, and in the subepithelial layer. Nerve fibers containing calcitonin gene-related peptide (CGRP) were numerous. They were distributed close to blood vessels, among bundles of muscle, in the subepithelial layer, and within the epithelium. A conspicuous finding was the occurrence of CGRP within motor end plates of striated muscle.
Dysphagia 1990
PMID:Neuropeptide-containing nerve fibers in the pharynx of the rabbit. 169 87

We review recent studies on the central neural control of esophageal motility, emphasizing the anatomy and chemical coding of esophageal pathways in the spinal cord and medulla. Sympathetic innervation of the proximal esophagus is derived primarily from cervical and upper thoracic paravertebral ganglia, whereas that of the lower esophageal sphincter and proximal stomach is derived from the celiac ganglion. In addition to noradrenaline, many sympathetic fibers in the esophagus contain neuropeptide Y (NPY), and both noradrenaline and NPY appear to decrease blood flow and motility. Preganglionic neurons innervating the cervical and upper thoracic ganglia are located at lower cervical and upper thoracic spinal levels. The preganglionic innervation of the celiac ganglion arises from lower thoracic spinal levels. Both acetylcholine (ACh) and enkephalin (ENK) have been localized in sympathetic preganglionic neurons, and it has been suggested that ENK acts to pre-synaptically inhibit ganglionic transmission. Spinal afferents from the esophagus are few, but have been described in lower cervical and thoracic dorsal root ganglia. A significant percentage contain calcitonin gene-related peptide (CGRP) and substance P (SP). The central distribution of spinal afferents, as well as their subsequent processing within the spinal cord, have not been addressed. Medullary afferents arise from the nodose ganglion and terminate peripherally both in myenteric ganglia, where they have been postulated to act as tension receptors, and, to a lesser extent, in more superficial layers. Centrally, these afferents appear to end in a discrete part of the nucleus of the solitary tract (NTS) termed the central subnucleus. The transmitter specificity of the majority of these afferents remains unknown. The central subnucleus, in turn, sends a dense and topographically discrete projection to esophageal motor neurons in the rostral portion of the nucleus ambiguous (NA). Both somatostatin-(SS) and ENK-related peptides have been localized in this pathway. Finally, motor neurons from the rostral NA innervate striated portions of the esophagus. In addition to ACh, these esophageal motor neurons contain CGRP, galanin (GAL), N-acetylaspartylglutamate (NAAG), and brain natriuretic peptide (BNP). The physiological effect of these peptides on esophageal motility remains unclear. Medullary control of smooth muscle portions of the esophagus have not been thoroughly investigated.
Dysphagia 1990
PMID:Central neural control of esophageal motility: a review. 220 57

Congenital esophageal stenosis (CES) is a rare disorder with narrowed esophageal lumen that presents as dysphagia from childhood and that is often associated with tracheobronchial remnants or webs. The pathogenesis of CES is unknown. The aim of this study was to examine the histological and immunohistochemical features of CES. Esophagi from 2 young adults with CES and 3 controls with no motility disorders underwent routine H&E staining, trichrome staining for collagen, and detailed immunocytochemical studies for general neuronal markers (protein gene product 9.5, neuron-specific enolase, and S-100) and neurotransmitters (vasoactive intestinal polypeptide, substance P, and galanin) and nitric oxide synthase by beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and a specific NO synthase antibody. Quantitative experiments compared the numbers of myenteric neurons and amounts of fibers at the circular muscle. CES esophagi showed infiltration of neutrophils in the myenteric plane, without any increase in collagen. NADPH-diaphorase histochemistry showed a significant reduction of myenteric nitrinergic neurons (7 +/- 3.4 vs. 2.7 +/- 1.8 neurons per high-power field) and fibers at the circular muscle. Other peptidergic neurons studied were not significantly reduced in CES. The specific total lack of NO inhibitory innervation may be an important mechanism in the pathogenesis of stenosis and aperistalsis of the esophagus in this disorder.
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PMID:Peptidergic and nitrinergic denervation in congenital esophageal stenosis. 754 Oct

Several neurotransmitters, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), galanin, enkephalin, calcitonin-gene related peptide (GGRP), substance P, as well as nitric oxide synthase (NOS), and the noradrenergic marker tyrosine-hydroxylase (TH) were localized by immunocytochemistry in the cervical esophagus of rat. Nerve fibers containing the neuropeptides, NOS, and TH were distributed in the myenteric plexus, around muscle bundles and small blood vessels. Injection of the retrograde tracer True Blue (TB) into the cervical esophagus resulted in the appearance of labeled nerve cell bodies in the superior cervical, the stellate, the nodose, the sphenopalatine, the dorsal root ganglia at levels C2-C7, and in local ganglia close to the thyroid. Most of the TB-labeled nerve cell bodies in the superior cervical ganglia contained NPY. In the stellate ganglion, a few labeled nerve cell bodies contained VIP whereas an additional few cell bodies stored VIP. In local ganglia, the majority of labeled cell bodies contained VIP. In the nodose ganglion and cervical dorsal root ganglia, the majority of the labeled nerve cell bodies stored CGRP. The results indicate that the cervical esophagus has a dense innervation with multiple neurotransmitters emanating from several ganglia. As judged by the pattern of nerve fiber distribution, they may regulate esophageal peristalsis and blood flow, some of them possibly in a cooperative manner.
Dysphagia 1995
PMID:Distribution and origin of the peripheral innervation of rat cervical esophagus. 754 92

Imidapril hydrochloride (imidapril) is a long-acting, non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor, which has been used clinically in the treatment of hypertension, chronic congestive heart failure (CHF), acute myocardial infarction (AMI), and diabetic nephropathy. It has the unique advantage over other ACE inhibitors in causing a lower incidence of dry cough. After oral administration, imidapril is rapidly converted in the liver to its active metabolite imidaprilat. The plasma levels of imidaprilat gradually increase in proportion to the dose, and decline slowly. The time to reach the maximum plasma concentration (T(max)) is 2.0 h for imidapril and 9.3 h for imidaprilat. The elimination half-lives (t(1/2)) of imidapril and imidaprilat is 1.7 and 14.8 h, respectively. Imidapril and its metabolites are excreted chiefly in the urine. As an ACE inhibitor, imidaprilat is as potent as enalaprilat, an active metabolite of enalapril, and about twice as potent as captopril. In patients with hypertension, blood pressure was still decreased at 24 h after imidapril administration. The antihypertensive effect of imidapril was dose-dependent. The maximal reduction of blood pressure and plasma ACE was achieved with imidapril, 10 mg once daily, and the additional effect was not prominent with higher doses. When administered to patients with AMI, imidapril improved left ventricular ejection fraction and reduced plasma brain natriuretic peptide (BNP) levels. In patients with mild-to-moderate CHF [New York Heart Association (NYHA) functional class II-III], imidapril increased exercise time and physical working capacity and decreased plasma atrial natriuretic peptide (ANP) and BNP levels in a dose-related manner. In patients with diabetic nephropathy, imidapril decreased urinary albumin excretion. Interestingly, imidapril improved asymptomatic dysphagia in patients with a history of stroke. In the same patients it increased serum substance P levels, while the angiotensin II receptor antagonist losartan was ineffective. These studies indicate that imidapril is a versatile ACE inhibitor. In addition to its effectiveness in the treatment of hypertension, CHF, and AMI, imidapril has beneficial effects in the treatment of diabetic nephropathy and asymptomatic dysphagia. Good tissue penetration and inhibition of tissue ACE by imidapril contributes to its effectiveness in preventing cardiovascular complications of hypertension. The major advantages of imidapril are its activity in the treatment of various cardiovascular diseases and lower incidence of cough compared with some of the older ACE inhibitors.
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PMID:Protection of the cardiovascular system by imidapril, a versatile angiotensin-converting enzyme inhibitor. 1217 88

Xeroderma pigmentosum group A (XPA) is a hereditary disorder characterized by cutaneous symptoms and progressive neurodegeneration. Since XPA patients exhibit peripheral neuropathy, neuronal deafness, rigidity, dysphagia, and laryngeal dystonia, it is indispensable for investigation of the neurodegeneration to analyze brainstem and basal ganglia lesions clinically and pathologically; we have previously shown the role of oxidative stress in the development of basal ganglia lesions. Here we immunohistochemically examined the expression of neurotransmitters, calcium-binding proteins, and neuropeptides in the brainstem, basal ganglia, and thalamus in 5 XPA autopsy cases. In the brainstem, immunoreactivity for tyrosine hydroxylase, tryptophan hydroxylase, and calbindin-D28K was severely reduced throughout the brainstem in all the XPA cases. Nevertheless, the expressions of parvalbumin, substance P, and methionine-enkephalin in the brainstem were comparatively preserved; the exception being reduced immunoreactivity for them in the cochlear and dorsal column nuclei in 3 cases. The large cell neurons in the putamen were preferentially reduced, the immunoreactivity for tyrosine hydroxylase reflecting the dopaminergic afferent and efferent pathways was severely affected, and the expression of 3 calcium binding proteins (i.e. parvalbumin, calbindin-D28K, and calretinin) was disturbed in various ways. The expression of substance P and methionine-enkephalin, which are involved in the efferent pathways in the basal ganglia, in the globus pallidus and substantia nigra was spared. It is speculated that the selective damage to the dopamine system in the basal ganglia and the disturbed monoaminergic expression in the brainstem could be related to clinical abnormalities such as the rigidity, laryngeal dystonia, and several neurophysiological changes. Functional analysis of autopsy brains will facilitate clarification of the pathogenesis of the neurodegeneration in XPA.
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PMID:Brainstem and basal ganglia lesions in xeroderma pigmentosum group A. 1553 32

Aspiration of the oropharyngeal or gastric contents by elderly persons often leads to lower respiratory tract infections, such as aspiration pneumonia or pneumonitis. The existence of dysphagia and aspiration in elderly patients are important factors in the occurrence of aspiration pneumonia, but are not sufficient to cause aspiration pneumonia in the absence of other risk factors. Salivary flow and swallowing can eliminate Gram-negative bacilli from the oropharynx in healthy persons. However, elderly persons may have diminished production of saliva as a result of medications and oral/dental disease, leading to poor oral hygiene and oropharyngeal colonisation with pathogenic organisms. When dysphagic patients aspirate pathogenic bacteria while swallowing food or liquids, they must also have decreased defences, such as impaired immunity or pulmonary clearance, in order to develop aspiration pneumonia.Elderly patients with cerebrovascular disease often have dysphagia that leads to an increased incidence of aspiration. It was previously reported that patients with silent cerebral infarction affecting the basal ganglia were more likely to experience subclinical aspiration and an increased incidence of pneumonia. Basal ganglia infarction leads to the impairment of dopamine metabolism and, as a consequence, a decrease of substance P in the glossopharyngeal nerve and sensory vagal nerves. Therefore, dysphagia and a decreased cough reflex may be induced by the impairment of dopamine metabolism in some elderly patients with cerebrovascular disease, suggesting that pharmaceutical agents which modulate dopamine metabolism may be able to improve swallowing and the cough reflex in patients with basal ganglia infarction. The main strategy for controlling aspiration and aspiration-related pulmonary infection in the elderly is to prevent aspiration of pathogenic bacteria along with the oropharyngeal or gastric contents. Because aspiration pneumonia in the elderly is related to certain risk factors, including dysphagia and aspiration, effective preventive measures involve various approaches, such as pharmacological therapy, swallowing training, dietary management, oral hygiene and positioning.
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PMID:Aspiration and infection in the elderly : epidemiology, diagnosis and management. 1573 19

Although clinically evident aspiration is common in subjects with dysphagia, a significant proportion may aspirate silently, i.e., without any outward signs of swallowing difficulty. This article reviews the literature on the prevalence, etiology, and prognostic significance of silent aspiration. An electronic database search was performed using silent aspiration, aspiration, dysphagia, and stroke as search terms, together with hand-searching of articles. Silent aspiration has been described in many conditions and subgroups of patients (including normal individuals), using a number of detection methods, making comparisons a challenge. The best data are for acute stroke, in which 2%-25% of patients may aspirate silently. Mechanisms associated with silent aspiration may include central or local weakness/incoordination of the pharyngeal musculature, reduced laryngopharyngeal sensation, impaired ability to produce a reflexive cough, and low substance P or dopamine levels. In terms of prognosis, silent aspiration has been associated with increased morbidity and mortality in many but not all studies. However, some degree of silent aspiration at night may be normal in healthy individuals. The phenomenon of silent aspiration is poorly understood and further research is needed to improve methods of detection and thereby better define its prevalence and prognostic significance.
Dysphagia 2005
PMID:Silent aspiration: what do we know? 1636 10

Understanding the innervation of the esophagus is a prerequisite for successful treatment of a variety of disorders, e.g., dysphagia, achalasia, gastroesophageal reflux disease (GERD) and non-cardiac chest pain. Although, at first glance, functions of the esophagus are relatively simple, their neuronal control is considerably complex. Vagal motor neurons of the nucleus ambiguus and preganglionic neurons of the dorsal motor nucleus innervate striated and smooth muscle, respectively. Myenteric neurons represent the interface between the dorsal motor nucleus and smooth muscle but they are also involved in striated muscle innervation. Intraganglionic laminar endings (IGLEs) represent mechanosensory vagal afferent terminals. They also establish intricate connections with enteric neurons. Afferent information is implemented by the swallowing central pattern generator in the brainstem, which generates and coordinates deglutitive activity in both striated and smooth esophageal muscle and orchestrates esophageal sphincters as well as gastric adaptive relaxation. Disturbed excitation/inhibition balance in the lower esophageal sphincter results in motility disorders, e.g., achalasia and GERD. Loss of mechanosensory afferents disrupts adaptation of deglutitive motor programs to bolus variables, eventually leading to megaesophagus. Both spinal and vagal afferents appear to contribute to painful sensations, e.g., non-cardiac chest pain. Extrinsic and intrinsic neurons may be involved in intramural reflexes using acetylcholine, nitric oxide, substance P, CGRP and glutamate as main transmitters. In addition, other molecules, e.g., ATP, GABA and probably also inflammatory cytokines, may modulate these neuronal functions.
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PMID:Innervation of the mammalian esophagus. 1657 41

Aspiration pneumonia is a major cause of death in patients with dysphagia, often accompanied by psychiatric symptoms. The inhibition of swallowing and cough reflexes, which contribute to a significant risk for aspiration, may be related to decreased levels of substance P. Clinical studies indicate a strong association of an increased mortality in psychiatric patients with the use of antipsychotics. The present study documented fewer positive episodes of swallowing reflex in patients treated with haloperidol for schizophrenia (7/11; 63.6%) than those treated with risperidone (10/11; 90.9%). In addition, patients treated with risperidone had serum substance P levels comparable with control subjects (29.0 +/- 7.8 pg/mL, 29.6 +/- 7.6, respectively; p = 0.9), while patients treated with haloperidol had significantly lower serum substance P levels (20.6 +/- 5.5 pg/mL; p < 0.01). Among patients on haloperidol, those with negative episodes of reflex (4/11; 36.4%) had serum substance P levels at 15.8 +/-1.0 pg/mL, in contrast with those with positive episodes (7/11; 63.6%) who had serum levels at 23.4 +/- 4.9 pg/mL. However, in the patient group treated with risperidone, serum substance P levels in the majority of patients with positive episodes of reflexes (10/11, 90.9%; 30.1 +/- 7.2 pg/mL) was found to be as high as in control subjects, all with positive episodes (5/5, 100%; 29.6 +/- 7.6 pg/mL) (p = 0.866), and higher than in one patient with negative reflex (1/11, 9.1%; 18.0 +/- 0.0 pg/mL). These results suggest that the decreased serum substance P levels are strongly associated with the use of haloperidol, as well as decreased swallowing reflexes. This suggests that serum substance P levels may be a useful predictive marker for the increased risk of developing aspiration, or subsequently aspiration pneumonia. Moreover, this increased incidence of aspiration may contribute to an increased mortality in patients following antipsychotic therapy. Risperidone, which has little influence on serum substance P productions, may be a more appropriate first-line drug of choice for treatment of schizophrenia.
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PMID:Serum substance P levels in patients with chronic schizophrenia treated with typical or atypical antipsychotics. 1872 97


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