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)

Adenosine and its derivatives enhanced the contractile responses to transmural nerve stimulation in rabbit isolated bronchial smooth muscle. 5'-N-Ethylcarboxamideadenosine (NECA) was the most potent adenosine analogue studied. Enhancement of contractile responses by NECA was competitively antagonized by 8-p-sulfophenyltheophylline. Guanethidine, mepyramine, capsaicin or eicosatetraynoic acid did not antagonize the enhancement elicited by adenosine or NECA. NECA did not enhance the contractile responses to exogenously applied acetylcholine or contractile responses elicited after administration of tetrodotoxin. We suggest that adenosine, via an action at A2 receptors, enhances contractile responses to nerve stimulation in rabbit bronchial muscle. Methylxanthines are competitive antagonists at these extracellular receptors. The enhancement probably involves a sodium-dependent mechanism but not adrenergic mechanisms or release of histamine, substance P or arachidonate metabolites. The enhancement indicates increased cholinergic transmitter release or action, but release of a secondary spasmogenic or decreased release of an inhibitor mediator cannot be excluded. The results may indicate a role for adenosine in asthma.
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PMID:Apparent enhancement of cholinergic transmission in rabbit bronchi via adenosine A2 receptors. 241 45

In addition to classical cholinergic and adrenergic neural mechanisms, a third division of autonomic control has been recognised in human airways. Non-adrenergic inhibitory nerves are the dominant inhibitory neural pathway in human airway smooth muscle and there is increasing evidence that VIP and a related peptide, PHM, may be the neurotransmitters. These peptides are probably cotransmitters of acetylcholine in the airways and may modulate cholinergic effects. A defect in this system could occur in asthma because inflammation may more rapidly inactivate these neurotransmitter peptides. Non-cholinergic excitatory nerves have also been described in animal airways, although their existence in human airways is less certain. The neurotransmitter may be substance P or a related peptide neurokinin A, which could be released by axon reflex. Another peptide, calcitonin gene-related peptide, is colocalized with substance P and appears to be much more potent in human airways. Non-adrenergic non-cholinergic mechanisms may also regulate mucus secretion and the bronchial microvasculature. The role of this nervous system in health and disease is still uncertain as there are no specific blockers available.
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PMID:Non-adrenergic non-cholinergic neural control of human airways. 242 61

Several peptides have been localised to pulmonary nerves and endocrine cells. The neuropeptides vasoactive intestinal polypeptide (VIP) and substance P have potent effects on the airway smooth muscle, bronchial glands and blood vessels. There is increasing evidence that VIP and substance P are neurotransmitters of the non-adrenergic, non-cholinergic nervous (NANC) system. Non-adrenergic inhibitory nerves are the predominant inhibitory nervous system of the human airways. The presence of VIP in the innervation of the airways and the demonstration that it can mimick the effect of NANC nerve stimulation supports the hypothesis that it could be a mediator of the NANC system in the lungs. Sensory nerve fibers containing substance P can contribute to the smooth muscle contraction and mucosal oedema seen in asthma, by local axon reflexes that are initiated by noxious stimuli, such as for example cigarette smoke. A rat model for study of the bronchial reaction to substance P and related tachykinins, is described. In addition to a direct effect on airway smooth muscle, a large part of the broncho-constrictory actions of tachykinins in the rat is mediated by interaction with cholinergic nerves.
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PMID:The respiratory effects of neuropeptides. 242 52

Several neuropeptides have now been localized to nerves in human airways and have marked effects on airway smooth muscle tone, bronchial blood flow, microvascular leakage, and airway secretions. There is mounting evidence that they may act as neurotransmitters of nonadrenergic, noncholinergic nerves and may be co-transmitters of classic autonomic nerves. Vasoactive intestinal peptide and the related peptide histidine methionine are potent relaxants of human airways in vitro, yet their effects in vivo are disappointing because of problems in delivery. Sensory neuropeptides such as substance P, neurokinins A and B, and calcitonin gene-related peptide may be involved in neurogenic inflammatory reactions in asthma. Although there have been no clinical benefits from these discoveries, in the future the development of agents that interfere with or mimic neuropeptide effects may offer novel therapeutic approaches to airway diseases such as asthma.
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PMID:Neuropeptides in human airways: function and clinical implications. 244 45

The peptides substance P (SP) and vasoactive intestinal peptide (VIP) released from peptidergic neurons have potent effects on gland secretion and on smooth muscle tone. Because mast cells release proteases during degranulation, and are located in many of the same tissue microenvironments into which SP and VIP are released, we wished to examine whether mast cell proteases, by cleaving and thus inactivating these peptides, could modulate their effects. We used active site-titrated preparations of the two major neutral proteases of mast cell granules, tryptase and chymase, to determine the sites and rates of cleavage of SP and VIP. The proteases were purified from dog mastocytomas. Tryptase cleaved VIP rapidly at two sites with a kcat/Km of 2.2 X 10(5) sec-1 M-1, but had no effect on SP. Chymase cleaved both SP and VIP at primarily a single site with kcat/Km of 3.9 X 10(4) and 5.4 X 10(4) sec-1 M-1, respectively. Thus, these data show that mast cell proteases degrade SP and VIP. The differences in peptidase activity between tryptase and chymase suggest that the consequences of protease release could vary according to mast cell protease phenotype and location in various tissues and species. Tryptase, by cleaving the bronchodilator VIP but not the bronchoconstrictor SP, might promote bronchial hyper-responsiveness in asthma by decreasing the nonadrenergic neural inhibitory influence mediated by VIP. In skin and other tissues, chymase might interrupt axon reflex-mediated neurogenic inflammation by cleaving SP.
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PMID:Substance P and vasoactive intestinal peptide degradation by mast cell tryptase and chymase. 244 73

1. We have studied the effect of the sensory neuropeptides substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and calcitonin gene-related peptide (CGRP) on microvascular permeability in guinea-pig airways in vivo and investigated whether CGRP would potentiate the effect of SP. We used the extravasation of intravenously-injected Evans blue dye as an index of permeability. 2. The tachykinins SP, NKA and NKB (0.025-5.0 nmol kg-1, i.v.) significantly (P less than 0.05) increased extravasation of dye in a dose-related manner and with a similar pattern of distribution; they were most potent in the trachea and main bronchi, less potent in the larynx and intrapulmonary airways, and had little significant effect in the bladder. 3. SP was significantly more potent in causing extravasation of dye than NKA or NKB with ED50 values (nmol kg-1) in the range 0.04-0.1, depending on the airway level, compared with values in the range 0.3-0.7 for the neurokinins. 4. CGRP (0.0025-2.5 nmol kg-1, i.v.) had no significant effect on microvascular permeability and did not potentiate SP-induced extravasation of dye. 5. Each neuropeptide decreased mean arterial blood pressure, indicating vasodilatation, in a dose-related manner. Co-injection of CGRP and SP produced additive decreases in arterial pressure. 6. We conclude that, in guinea-pig airways, tachykinins increase microvascular permeability via tachykinin receptors of the NK-1 sub-type (indicated by an order of potency of SP greater than NKA = NKB) on endothelial cells. The response appears to be related to mechanisms in addition to vasodilatation. The relevance of the responses to the tachykinins in asthma is discussed.
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PMID:Effects and interactions of sensory neuropeptides on airway microvascular leakage in guinea-pigs. 246 89

Opioid drugs have been shown to inhibit neurogenic plasma exudation in skin by a presynaptic mechanism. We determined whether a similar inhibitory effect operates in the airways of anesthetized guinea pigs in vivo with the use of Evans blue dye as a marker of plasma leakage. Stimulation of the vagus nerve significantly increased leakage of dye in trachea and main bronchi (by approximately 300 and 600%, respectively). Similar increases in leakage were seen in the presence of atropine and propranolol. Morphine (1-30 mg/kg iv) inhibited leakage in a dose-related manner with complete inhibition in the trachea at a dose of 30 mg/kg. The inhibition was blocked by the opioid receptor-antagonist naloxone (1 mg/kg iv). Intravenous substance P significantly increased leakage but was not inhibited by morphine. We conclude that morphine inhibits neurogenic plasma leakage by presynaptic inhibition of release of neuropeptides from sensory nerve endings. If similar mechanisms are operative in human airways, inhibition of neurogenic plasma leakage by opioid drugs devoid of central effects may be of value in the therapy of asthma.
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PMID:Neurogenic plasma extravasation: inhibition by morphine in guinea pig airways in vivo. 246 90

The neuropeptide substance P modulates the activities of a number of different leukocytes that characterize both acute and delayed inflammatory responses. Substance P may play a role in the pathogenesis of such diverse diseases as arthritis, asthma, and inflammatory bowel disease.
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PMID:Neuropeptides and inflammation: the role of substance P. 247 50

Substance P (SP) is localized in sensory nerves of the respiratory tract in close connection to the effector cells of inflammatory and allergic bronchial diseases. SP is proposed to play an important role in the pathogenesis of bronchial asthma because of its ability to induce bronchoconstriction, vasodilatation and an edema of the mucous membrane and to enhance the secretion of tracheobronchial glands. Furthermore inflammatory and immune cells are influenced by SP. SP seems to have a complex action in the regulation of the bronchial tonus. Especially differences in the action of partial sequences of the peptide may be important in the pathogenesis of asthma.
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PMID:[The role of substance P in regulating bronchomotor tone and the pathogenesis of bronchial hyperreactivity]. 247 22

Pulmonary hyperreactivity is a common feature in asthma. In the present study we investigated the possible role of different mediators in the genesis of this phenomenon. In particular the ability of prostaglandin D2 (PGD2), substance P (SP) and bradykinin (BK) to potentiate acetylcholine (ACh)-induced bronchospasm was assessed in anaesthetized and mechanically ventilated guinea-pigs. Threshold doses of PGD2, SP and BK significantly enhanced ACh-induced bronchospasm in normal guinea-pigs, even if a different trend in the onset and duration of the phenomenon was observed. Ovalbumin (OA) active sensitization modified the ability of the three compounds tested to positively interact with ACh. Beta-adrenoceptor blockade due to propranolol treatment increased the positive interaction between the three compounds and ACh. The role of PGD2, SP and BK in the genesis of pulmonary hyperreactivity is proposed and the relevance of mediator-mediator interaction during adrenergic imbalance is discussed.
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PMID:Role of the mediators in pulmonary hyperreactivity: the cocktail interaction hypothesis. 247 37


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