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)

Nedocromil sodium is a new chemical entity. This compound is very hydrophilic and is well absorbed by tissues such as the lung but not by tissues with tight junctions such as the gut. This product is chemically different from all drugs currently used for the treatment of airway diseases. The in vitro effects of nedocromil sodium are reviewed. Nedocromil sodium is capable of blocking: 1) the chemotaxis of neutrophils; 2) the activation of macrophages and monocytes by IgE; 3) the release of histamine from mast cells; 4) the cytotoxicity of platelets; 5) the release of LTC4 from eosinophils. Nedocromil sodium thus seems to have an effect on each of the cells which are implicated in the allergic reactions. In animals, nedocromil sodium can block the immediate bronchoconstriction induced by an antigen, adenosine and neurokinin A. Nedocromil sodium can also block the increase in bronchial responsiveness induced by antigen exposure. Moreover, vascular permeability induced by ovalbumin is reduced by nedocromil sodium. In summary, nedocromil sodium demonstrated a significant inhibitory effect of inflammation in both in vivo and in vitro models.
Rev Mal Respir 1992
PMID:[Basic research on nedocromil sodium]. 131 52

An understanding of the non adrenergic non cholinergic nervous system and its implication in the pathogenesis of asthma would benefit by the identification and localisation of the numerous natural bioactive peptides at the pulmonary level. In the past few years two components of the non adrenergic non cholinergic nervous system have been characterised. A bronchodilator component which would be mediated by "vaso-active intestinal peptide" (VIP) and the "peptide histidine methionine" (PHM). A broncho-constrictor component which would be mediated by the neurokinins (substance P (SP), neurokinin A (NKA) and the "calcitonin gene related peptide" (CGRP)). These neuropeptides, in vitro as well as in vivo, have effects which are not limited to the regulation of bronchial smooth muscle tone. In effect, they may intervene in the regulation of vascular tone, in the production of mucous and in the expression of immediate hypersensitivity reactions at pulmonary level. Several neuropeptides are present or co-exist with classical neurotransmitter in the afferent nerve endings of the pulmonary efferents. This co-existence of several neurotransmitters in the same nervous fibres raised the questions as to their interactions at the pre or post synaptic level. The implication of these neuropeptides in the pathogenesis of asthma rests on numerous experimental arguments. This recent aspect in the pathophysiology of asthma allows us to hope for new therapeutic approaches.
Rev Mal Respir 1988
PMID:[The nonadrenergic, noncholinergic neuropeptide system and asthma]. 289 31

Endothelial cells of the arterial wall can generate vasodilator and vasoconstrictor substances. The prototype of a vasodilator substance formed primarily in the endothelium is prostacyclin, although its main target under physiological conditions are the platelets. In addition, the endothelial cells respond to a variety of neurohumoral mediators by the liberation of an unidentified substance(s) (endothelium-derived relaxing factor) with a potent inhibitory effect on vascular smooth muscle, presumably because it accelerates the production of cyclic GMP in the latter. Endothelium-derived relaxing factor is very unstable, and has an extremely short half-life. It is inactivated by plasma proteins and thus does not fulfill a hormonal role. A metabolite of arachidonic acid may be involved in the production of endothelium-derived relaxing factor. Among the neurohumoral mediators which release it are: acetylcholine (through activation of muscarinic receptors), adenosine di- and triphosphate (P2-purinergic receptors), bradykinin, histamine (H1- or H2-histaminergic receptors, depending on the species), serotonin (S1-serotonergic receptors), substance P, oxytocin, thrombin and vasopressin (V1-vasopressinergic receptors). The release of the factor can also be triggered by aggregating platelets (because they release adenine nucleotides and serotonin) and by increases in shear stress. It is likely that endothelium-dependent dilatation helps to prevent intraluminal coagulation in arteries with a normal intima. Absence, or dysfunction of the endothelium may favor the occurrence of vasospasm. Endothelium-dependent relaxations are reduced in atherosclerotic blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mal Vasc 1986
PMID:[The endothelium and arterial reactivity]. 349 May 30

Airway responsiveness is increased in a variety of airway diseases. To understand the mechanism of enhanced airway responsiveness, in particular as it pertains to asthma, animal models have been developed and extensively explored. The guinea pig and Basenji-greyhound dog are the best characterized animals showing airways hyperresponsiveness and appear to bear substantial resemblances to asthmatic human subjects. Challenge with bronchoconstrictive agonist results in bronchoconstriction and transient vascular leak. Both phenomena contribute to the degree of airway narrowing. Adenosine challenge tests not only the responsiveness of the airways, but also that of the airway effector cells such as the mastocyte. Bradykinin and tachykinin cause indirect airway narrowing, probably by liberation of leukotrienes. Responsiveness can be enhanced by immune and non-immune challenges. Ozone, Sephadex, various contractile agonists (leukotriene D-4, bradykinin, platelet-activating factor), as well as certain cytokines (IL-1, IL-2, TNF-alpha) can enhance airway responsiveness. Cyclooxygenase and lipooxygenase products appear to be involved. Allergen-induced hyperresponsiveness is associated with airway inflammation and appears to involve bradykinin and PAF acutely and growth of airway smooth muscle chronically.
Rev Mal Respir 1994
PMID:[Animal models of bronchial hyperreactivity]. 751 8

In the last decade, several neuropeptides have been localized in sensory, sympathetic and parasympathetic neurons of the upper and lower airways in animals and man. Tachykinins are sensory neuropeptides: after nasal allergen challenge in patients with allergic rhinitis, substance P is locally released and induces nasal obstruction. Like neurokinin A, another tachykinin of sensory C fibers, substance P induces an increase in vascular permeability and a recruitment of inflammatory cells. Thus, tachykinins partially mimic nasal response to antigen. Calcitonin gene-related peptide (CGRP) is another sensory neuropeptide and vasoactive intestinal peptide (VIP) is a neuropeptide localized to parasympathetic fibers. The distributions of CGRP and VIP fibers and of their binding sites, as well as their physiological effects described in other tissues, are consistent with a vasodilator effect. On the other hand, neuropeptide Y (NPY), a sympathetic neuropeptide, would seem to be a potent vasoconstrictor. Thus, nasal neuropeptides, and above all sensory neuropeptides, could play a role in the pathophysiology of allergic rhinitis.
Rev Mal Respir 1994
PMID:[Neuropeptides of the nasal innervation and allergic rhinitis]. 752 27