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 mechanism of action of xanthines in asthma remains controversial. Since sensory innervation may play a role in the pathogenesis of asthma, we investigated whether xanthines were capable of reducing the contractile response of the bronchi to nerve stimulation. In guinea-pig bronchi in vitro, electrical field stimulation (EFS: 40 V, 16 Hz, 0.2 ms during 10 s) induces a rapid cholinergic contraction followed by a long-lasting contraction due to a local release of neuropeptides from C-fibre endings. We measured isometric neuronally-mediated contractions of bronchial smooth muscle and studied the effects of increasing concentrations of two xanthine derivatives, theophylline, an antagonist of adenosine receptors, and enprofylline, which has no effect on adenosine receptors. Both enprofylline (1-50 microM) and theophylline (10-100 microM) inhibited, in a concentration-dependent manner, the peptidergic contraction, an effect which was more marked with enprofylline than theophylline (EC50 = 9.6 +/- 0.7 microM and 62.0 +/- 4.7 microM, respectively). Conversely, the cholinergic response was unaffected. Contractions induced by exogenous substance P (0.03-3 microM) were also unaffected by theophylline and enprofylline at the above mentioned EC50s. Our results suggest that concentrations of theophylline, similar to those used therapeutically, reduce the release of sensory neuropeptides from C-fibre endings. This effect is unrelated to adenosine receptor blockade, since enprofylline had a similar inhibitory effect.
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PMID:Modulation by theophylline and enprofylline of the excitatory non-cholinergic transmission in guinea-pig bronchi. 148 66

The Biopsychosocial Approach (BPSA) is a treatment program for allergic patients which includes therapy for psychological, behavioral and social factors as well as for physical problems, following basic principles of psychoneuroimmunology. BPSA was applied to patients with bronchial asthma and favorable results were obtained. The mechanism of the therapeutic effects of BPSA included normalization of the patient's autonomic nervous function, levels of blood histamine, and circadian rhythm of lymphocyte activity. BPSA was also used in patients with exercise induced asthma (EIA) and the same parameters were evaluated. Results showed that patients with EIA recovered physiological homeostasis after BPSA therapy normalized blood levels of histamine and substance P (SP), skin reactions to histamine and SP, and autonomic nervous function. We conclude that BPSA is effective for treating patients with EIA.
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PMID:Effects of the biopsychosocial approach (BPSA) on exercise-induced asthma (EIA). 154 87

The tracheobronchial vasculature consists of a subepithelial capillary network and a deeper system of blood sinuses or capacitance vessels. There seem to be no arteriovenous anastomoses. Sympathetic nerves constrict the vasculature by the transmitters noradrenaline and neuropeptide-Y, parasympathetic nerves dilate it by acetylcholine and vasoactive intestinal polypeptide, and sensory nerves release neuropeptides including substance P that are dilator. Most inflammatory mediators are also vasodilator. In asthma there is mucosal vasodilation due to the direct action of mediators on vascular smooth muscle, neuropeptides released by axon reflexes in sensory nerve receptors, and possibly reflex vasodilation due to stimulation of sensory nerves. The vasodilation increases the thickness of the mucosa, both by vascular engorgement and by increased interstitial liquid volume. This mucosal thickening will narrow the airways and increase the rigidity of their walls. The vascular bed is also dilated by cold and hyperosmolality, and this change may be a component of the bronchoconstriction due to hyperventilation, inhalation of cold air and exercise. Changes in mucosal blood flow influence the uptake of chemical agents from the lumen, and the success of aerosol therapy in asthma may to some extent depend upon the influence of mucosal blood flow.
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PMID:Asthma. Tracheobronchial vasculature. 161 86

1. The ability of cromakalim to modulate several different types of neuroeffector transmission has been assessed in guinea-pig isolated trachea. 2. In trachea treated with propranolol (10(-6) M) and indomethacin (2.8 x 10(-6) M), stimulation of the extrinsic vagal nerves evoked contractions which were blocked by hexamethonium (5 x 10(-4) M) or by tetrodotoxin (TTX; 10(-6) M). Cromakalim (10(-5) M) caused a two fold rightward shift of the frequency-response curve. 3. In carinal trachea treated with propranolol and indomethacin, transmural stimulation evoked an initial, rapid contraction followed by a more sustained secondary contraction. The initial, rapid contractile response was virtually ablated by atropine (10(-6) M) or by TTX but was resistant to hexamethonium. Cromakalim (10(-8)-10(-5) M) caused a concentration-dependent rightward shift of the frequency-response curve for the initial contraction. 4. In carinal trachea treated with atropine, propranolol and indomethacin, transmural stimulation evoked only the secondary (non-adrenergic, non-cholinergic (NANC] contractile responses. These were markedly reduced by TTX but were resistant to hexamethonium. Cromakalim (10(-8)-10(-5) M) suppressed the NANC contractile responses in a concentration-dependent manner. This action could be offset by glibenclamide (10(-6) M). 5. In trachea treated with atropine, histamine (10(-4) M), propranolol and indomethacin, transmural stimulation evoked NANC relaxant responses. Cromakalim (up to 10(-5) M) was without effect on the frequency-response curve for the stimulation of NANC inhibitory nerves. 6. Tested on trachea bathed by drug-free Krebs solution, cromakalim (10(-7)-10(-5) M) caused concentration-dependent suppression of tracheal tone. In trachea treated with propranolol and indomethacin, cromakalim (10- 7-1O- 5 M) caused concentration-dependent antagonism of acetylcholine (ACh). In trachea treated with atropine, propranolol and indomethacin, cromakalim (up to 10- 5M) failed to antagonize effects of either histamine or substance P.7. It is concluded that cromakalim can inhibit cholinergic (excitatory) neuroeffector transmission in the trachea but only at a concentration having demonstrable inhibitory activity against the action of exogenous ACh and the spontaneous tone of the airways smooth muscle. In contrast, cromakalim may depress NANC excitatory (putative peptidergic) neuroeffector transmission at a concentration below that exerting inhibitory activity on airways smooth muscle. Cromakalim does not concurrently depress NANC inhibitory neuroeffector transmission. Depression of NANC excitatory neuroeffector transmission could explain the ability of cromakalim to suppress airway hyperreactivity or bronchial asthma at doses lacking direct relaxant effect on airways smooth muscle.
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PMID:Effects of cromakalim on neurally-mediated responses of guinea-pig tracheal smooth muscle. 166 64

The purpose of the present study was to evaluate the modulatory effects of sensory neuropeptides on peripheral blood mononuclear leukocytes of normal and allergic subjects. Peripheral blood mononuclear leukocytes obtained from five normal subjects and from five patients with allergic rhinitis and asthma were incubated with morphine, ACTH, vasoactive intestinal peptide, or substance P at concentrations of 10(-9) M, 10(-7) M, 10(-6) M and suboptimal (0.0125 microgram/mL, 0.025 microgram/mL, and 0.05 microgram/mL) concentrations of PHA. Uptake of 3H-thymidine was evaluated at 72 hours of culture. An inhibitory effect was observed with morphine, ACTH, and substance P while stimulatory effects were seen with vasoactive intestinal peptide, both in normal and in allergic subjects. The results of these preliminary studies provide further evidence for a modulatory role of neuropeptides on the immune function in both normal and allergic subjects.
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PMID:In vitro studies of the modulatory effects of sensory neuropeptides on peripheral blood mononuclear leukocytes of normal and allergic subjects. 168 92

Electrical field stimulation of sensitized guinea pig hilus bronchi induced a long lasting contractile response which was insensitive to atropine, but could be antagonized by a substance P (SP) antagonist. Antigen challenge of sensitized guinea pig main and hilus bronchi evoked a double-phase contractile response which consisted of a rapid contraction and a slow contraction. Both of them were sensitive to SP-antagonist, especially its slow contraction. Disodium cromoglycate (DSCG) inhibited the contractile responses induced by electrical field stimulation and antigen challenge. significantly. These results suggest that DSCG has inhibitory effect on the release of SP sensory nerve fibre endings induced by some stimulators, which might be related to the effect of DSCG against asthma.
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PMID:[The inhibitory effect of disodium cromoglycate on substance P sensory nerve fibres]. 169 25

Several lines of evidence suggest a possible role for mast cell proteases in modulating the biologic effects of neuropeptides. To explore the potential of such interactions in human airway, we examined the activity of human tryptase, the major secretory protease of human lung mast cells, against several neuropeptides with proposed regulatory functions in human airway. Using highly purified tryptase obtained from extracts of human lung, we determined the sites and rats of hydrolysis of vasoactive intestinal peptide (VIP), peptide histidine-methionine (PHM), calcitonin gene-related peptide (CGRP), and the tachykinins substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). Tryptase hydrolyzes VIP rapidly at several sites (Arg12, Arg14, Lys20, and Lys21) with an overall kcat/Km of 1.5 x 10(5) M-1 s-1 and hydrolyzes PHM primarily at a single site (Lys20) with a kcat/Km of 1.9 x 10(4) M-1 s-1. Tryptase also rapidly hydrolyzes CGRP at two sites (Arg18 and Lys24) with a kcat/Km of 2.7 x 10(5) M-1 s-1. The tachykinins are not hydrolyzed by tryptase. These observations raise the possibility that tryptase-mediated degradation of the bronchodilators VIP and PHM combined with exaggerated mast cell release of tryptase may contribute to the increase in bronchial responsiveness and the decrease in immunoreactive VIP in airway nerves associated with asthma. The favorable rates of hydrolysis of CGRP suggest that tryptase may also terminate the effects of CGRP on bronchial and vascular smooth muscle tone and permeability.
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PMID:Degradation of airway neuropeptides by human lung tryptase. 169 72

Further evidence is reported on the influence exerted by capsaicin on the anaphylactic reaction evoked in actively sensitized guinea-pigs. In Herxheimer microshock induced by ovalbumin aerosol, pretreatment of animals with 100 micrograms/kg i.p. capsaicin prolonged the preconvulsion time when the drug was administered 3 h before antigen challenge. In contrast, the same dose of capsaicin injected 30 min before aerosol caused a shortening of latency of the respiratory symptomatology. The influence of the drug is no longer evident after 24 h. In "in vitro" experiments desensitization to capsaicin of tracheal preparations caused a reduction of histamine and SRS-A released during antigen challenge, in comparison to controls. Moreover, anaphylactic histamine release was increased in preparations perfused with 10(-8) M substance P. In conclusion, our findings confirm that neuropeptides may be involved in the pathogenesis of asthma by affecting release of mediators.
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PMID:Capsaicin and anaphylactic reactions in the guinea-pig airways. 169 70

Substance P (SP) is one of the endogenous tachykinin peptides implicated in neurogenic inflammation and may be critically involved in diseases as diverse as asthma, arthritis and inflammatory bowel disease. The current study was initiated to identify a rich source of SP receptor that would be amenable for studying the regulatory mechanism of the receptor. By using a radioligand receptor binding technique, sheep ileal smooth muscle membranes showed a much higher density of [3H]SP specific binding than other non-neural rat or sheep tissues and organs surveyed. Of the protease inhibitors tested, only phosphoramidon, a specific and potent enkephalinase inhibitor, prevented the degradation of [3H]SP and enhanced [3H]SP binding to the membrane. [3H]SP binding to the specific binding sites in the membranes was time-dependent and reached a steady state after 60 min at 22 degrees C in 25 mM Tris.NH3 (pH 7.4). Calcium and magnesium ions enhanced [3H]SP specific binding. Saturation binding studies showed that the dissociation constant (KD) and the density of maximum binding sites for [3H]SP specific binding were 0.54 nM and 83 fmol/mg of protein, respectively. The specificity of the [3H]SP labeled sites was SP greater than (4-11) SP greater than eledoisin greater than spantide greater than neurokinin-A greater than D-Pro2D-Phe7D-Trp9-SP. Neurokinin-B and senktide showed no inhibition of [3H]SP binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification and characterization of the substance P receptor in sheep intestinal smooth muscle membranes. 169 67

We studied substance P-induced cutaneous and bronchial reactions in children with allergic disorders. Furthermore, inhibitory effects of lidocaine on these responses elicited by substance P were also studied. In the intradermal test, children with moderate or severe bronchial asthma showed significantly stronger reactions than controls. In bronchial challenge with substance P, children with bronchial asthma showed an increasing fall in FEV1 and V50 in proportion to the severity of their asthma. Concomitant use of lidocaine significantly inhibited not only substance P-induced intradermal erythema and wheal reactions but air flow limitations. It also inhibited histamine-induced erythema and house dust-induced wheal and erythema reactions. No adverse reactions to lidocaine were observed. These results suggest that substance P might play an important role in cutaneous and bronchial hypersensitivity reactions in humans and that lidocaine has an inhibitory effect on substance P-induced reactions.
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PMID:Substance p-induced cutaneous and bronchial reactions in children with bronchial asthma. 170 91


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