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 release of neurotransmitters may exacerbate the inflammatory response. Such neurogenic inflammation has been documented in a number of inflammatory diseases. Neurogenic inflammation due to release of neuropeptides from sensory nerves has been demonstrated in airways of several species, particularly rodents, and may contribute to the inflammatory response in asthmatic airways. Tachykinins (substance P and neurokinin A) released from airway sensory nerves may cause bronchoconstriction, vasodilatation, plasma exudation, and mucus secretion, whereas another sensory neuropeptide, calcitonin generelated peptide, may contribute to hyperemia of inflammation. Airway epithelial damage in asthma exposes sensory nerves which may become sensitized by inflammatory products (including prostaglandins and cytokines) so that neuropeptides are released via a local reflex trigger such as bradykinin, resulting in exaggerated inflammation. The effects of tachykinins may be amplified further by loss of the major degrading enzyme, neutral endopeptidase, from epithelial cells. Direct evidence for neurogenic inflammation in asthma is still awaited, however. Several strategies for reducing neurogenic inflammation are possible, particularly inhibition of neuropeptide release from sensory nerves by stimulating prejunctional receptors such as mu-opioid receptors.
J Asthma 1992
PMID:Neurogenic inflammation and asthma. 135 Oct 52

Substance P elicits histamine release from human skin and rodent mast cells. Since neuropeptide-mediated reflexes may be important in asthma, we examined the ability of substance P to stimulate human mast cells obtained at bronchoalveolar lavage (BAL). BAL samples were obtained at routine bronchoscopy from 35 non-preselected patients. Histamine release experiments were performed in a standard manner using substance P and the calcium ionophore A23187. Both substance P (50 microM) and A23187 caused histamine release (median 26.7% range 6.2-62.8% and 32.1%, 7.7-56.8% respectively) which was significantly greater (P < 0.0001) than the spontaneous release (median 15.6%, range 4.1-33.4%), i.e. that in the absence of any stimulus. Substance P induced histamine release was via an energy dependent process and was blocked by preincubation with antimycin A. A significant correlation was observed between substance P induced release and spontaneous release but was not observed with A23187 induced release. Mast cell counts correlated significantly with substance P induced release but not with spontaneous or A23187 induced release. The substance P induced histamine secretion was elicited at similar concentrations to those used with rodent and human skin mast cells. Asthma is associated with increased numbers of mast cells which have both increased spontaneous and stimulated secretory responses. Thus, in vivo, the bronchoconstrictor action of substance P may in part result from activation of mast cells in the bronchial lumen.
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PMID:Substance P induces histamine release from human pulmonary mast cells. 753 43

The complex interaction of neurotransmitters, vascular supply, and mucociliary function constitute one of the main defense mechanisms of the respiratory tract, modulating airflow and response to noxious assault. One of the main controls of airflow relies upon the modulation of vasodilation and vasoconstriction via the autonomic control of a sinusoid system. In addition to noradrenaline and acetylcholine, an ever-increasing number of neurotransmitters are involved, including neuropeptide Y, vasoactive intestinal peptide, peptide histidine leucine, substance P, and calcitonin gene-related peptide. The existence of a reciprocating cycle of congestion and decongestion has been recognized for over a century, although its exact function is unknown. Recent studies using acoustic rhinometry have demonstrated that the cycle is present in some form in the majority of adults, in children as young as 3 years, and that it persists after cessation of nasal airflow. It may, however, be overridden or modulated by many environmental and pathological situations. By contrast, the defense function of mucociliary clearance is well-established, and while also subject to environmental influences, relies upon an innate and cyclical pattern of mucus flow from within the sinuses and nasal cavity into the oropharynx. The content of the mucus is fundamental to its protective function and the control of mucociliary clearance intimately related to autonomic activity.
Allergy Asthma Proc
PMID:Nasal physiology: neurochemical receptors, nasal cycle, and ciliary action. 887 35

During inflammatory states, airway epithelial cells are stimulated by various proinflammatory mediators to synthesize paracrine mediators including prostaglandin E2, which likely contributes to the recurrence of allergic inflammation. We studied the effects of acetylcholine (ACh) and substance P (SP) on PGE2 release because these two neuromediators are widely involved in airway inflammation, e.g., to trigger mucosal vasodilation and plasma exudation. PGE2 release was studied at baseline and after addition of ACh and SP (10(-10) to 10(-7) M) in primary cultures of human nasal epithelial cells from control mucosa, inflammatory non-atopic mucosa, and inflammatory atopic mucosa. The mediators' effects on COX 2 mRNA were assessed by Northern blotting. We also tested the effect of atropine and SR140333, inhibitors of ACh and SP, respectively. The spontaneous release of PGE2 was about three times higher in cells from atopic subjects. ACh and SP markedly increased PGE2 release (by more than 1.5 times) and this effect was similar whether the sampled tissues were inflammatory or not. In cells from atopic subjects this neuromediator effect led to a fivefold increase in PGE2 release, as compared to baseline production by cells from control mucosa. This stimulation of PGE2 release by neural mediators was inhibited by specific antagonists. ACh and SP increased COX 2 mRNA in the three groups. Thus, neuromediators can bolster PGE2 production in the airway, likely reinforcing inflammation. In conclusion, these data provide evidence that the interplay of nerve fibers and airway epithelial cells is likely important in inflammatory conditions as, e.g., allergy and asthma.
Allergy Asthma Proc
PMID:Neural-epithelial cell interplay: in vitro evidence that vagal mediators increase PGE2 production by human nasal epithelial cells. 1122 12

Nasal sensory nerve stimulation leads to sensations of pain and congestion and nociceptive nerve axon response-mediated release of substance P that stimulates glandular secretion as an immediate-acting protective mucosal defense. Recruited parasympathetic reflexes cause submucosal gland secretion via muscarinic M3 receptors. Parasympathetic reflexes, sneezing, and other avoidance behaviors rapidly clear the upper airway of offending agents while protecting the lower airways. Dysfunction contributes to allergic, infectious, and other nonallergic rhinitides and possibly sinusitis. Sympathetic arterial vasoconstriction reduces mucosal blood flow, sinusoidal filling, and mucosal thickness, restoring nasal patency. Loss of sympathetic tone may contribute to some chronic, nonallergic rhinopathies.
Curr Allergy Asthma Rep 2001 May
PMID:Neurogenic mechanisms in rhinosinusitis. 1189 43

Neural regulation of the airways consists of cholinergic excitatory, adrenergic inhibitory nerves and nonadrenergic, noncholinergic (NANC) nerves. NANC nerves can be either inhibitory or excitatory. Cholinergic nerves form the predominant bronchoconstrictor neural pathway in human airways. Acetylcholine controls neuronal and nonneuronal target cells via a short-lived action at nicotinic and muscarinic receptors. The most important control over acetylcholine release from postganglionic cholinergic nerves is exerted by acetylcholine itself. The M2 autoreceptor is located prejunctionally on postganglionic nerves. Its stimulation limits the further release of acetylcholine. A loss of function in the neuronal muscarinic M2 autoreceptor occurs after exposure to allergen, ozone, or viruses. In human airways, inhibitory NANC (i-NANC) mechanisms are the only neural bronchodilatory mechanisms. The presumed neurotransmitters of the i-NANC system are vasoactive intestinal peptide and nitric oxide. Substance P and neurokinin A have been implicated as the neurotransmitters mediating the excitatory part of the NANC nervous system. NK2 receptors are present on smooth muscle of both large and small airways and mediate part of the bronchoconstrictor effect of tachykinins. Most of the proinflammatory effects of substance P are mediated by the NK1 receptor. Tachykinin receptor antagonists are currently being developed as a possible anti-asthma treatment. An extensive cross-talk exists between nerves and the immune system. The complexity of the picture has increased further as it has become clear that classical neurotransmitters, such as acetylcholine and neuropeptides, are produced by nonneuronal cells.
Curr Allergy Asthma Rep 2001 Mar
PMID:The role of neuroeffector mechanisms in the pathogenesis of asthma. 1189 96

Pain and itch sensations are induced by depolarization of distinct populations of unmyelinated type C, and possibly other, neurons. Both sets of neurons and sensations serve critical protective mechanisms that maintain the integrity and patency of the upper airways. When noxious or pruritic stimuli are applied on the afferent nerve ending, pain and itch are appreciated at the thalamic and parietal cortex. In the mucosa, this neuronal depolarization spreads via the peripheral efferent axon response mechanism. Neuropeptides such as substance P and calcitonin gene-related peptide are released from neurosecretory varicosities on the nociceptive C fibers. The exact functions of axon responses differ between humans and rodents, and in health and disease. Separate itch- and pain-specific peripheral type C fibers, secondary relay interneurons in the spinal cord dorsal horn, anatomical locations in the lateral spinothalamic tract, and thalamic nuclei demonstrate that all nociceptive nerves are not the same. Other types of irritant-sensitive trigeminal neurons might be discovered that could mediate other unique sensations, specific axon responses, or central nervous system functions.
Curr Allergy Asthma Rep 2003 May
PMID:A tale of two neurons in the upper airways: pain versus itch. 1266 70

Asthma represents a chronic inflammatory process of the airways. The neurothrophin (NGF) and neuropeptides such as substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) play important role in stimulation of airways inflammation in asthmatics. NGF stimulates the differentiation and the migration of mast cells to bronchi epithelium. Furthermore, NGF stimulates mast cell degranulation and mediator upregulation and release. It also influences activity of basophils, eosinophils, neurophils, macrophages and T-cells. In addition, its important role in releasing of hyperresponsiveness has been proved. Neuropeptides such as CGRP and SP stimulate migration and degranulation of eosinophils and influence on airway responsiveness in asthmatics. This review article discusses the neuropeptides and NGF actions and mechanisms in the pathogenesis of asthma.
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PMID:[Role of neurotrophin and neuropeptides in bronchial asthma]. 1517 88

Neuropeptides, possessing specific and functional receptors on various cells of the immune system, have the potential to regulate immune responses; and the macrophages as important components of defense against various agents, are at their influence. In this study the effect of neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) on IL-1 beta production by herpes simplex type-1 (HSV-1)-infected and also uninfected mouse peritoneal macrophages were considered. Each neuropeptide separately has upregulated IL-1 beta production by HSV- 1 infected macrophages with the greatest effect at the concentrations of 1 09M for both SP and CGRP, but no synergistic effect on IL-1 production has been observed in the presence of both neuropeptides at optimal concentrations. IL-113 production by uninfected macrophages was also moderately enhanced in the presence of each neuropeptide, but not in the presence of both neuropeptides simultaneously. It can be concluded that IL-1 beta production, which is part of macrophage mediated inflammatory response to HSV-l, is enhanced by specific doses of neuropeptides.
Iran J Allergy Asthma Immunol 2003 Jun
PMID:Neuropeptides (sp and CGRP) augment IL-1 Beta production in hsv-infected macrophages. 1730 63

Pruritus is synonymous with itching. Many medical conditions are complicated by chronic pruritus compromising the patient's quality of life. The majority of pruritic stimuli are transmitted through C fibers into the lateral spinothalamic tract and then into the somatic sensory cortex where the itching is detected. Histamine, substance P, and tumor necrosis factor a play significant roles in the perception of pruritus. Medical conditions in adults with significant pruritus will be defined in this review.
Allergy Asthma Proc
PMID:What lies beneath the surface of the itch in adults? 1747 98


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