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)

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

Activation of cutaneous sensory nerves induces vasodilatation and vascular permeability, i.e., neurogenic inflammation. We examined the histology and possible mast cell involvement in cutaneous neurogenic inflammation induced by electrical nerve stimulation (ENS). Three lines of evidence indicated that mast cells were not involved in rodent cutaneous neurogenic inflammation induced by electrical stimulation of the saphenous nerve. 1) Most mast cells (86.5% of all mast cells in the dorsal skin of the paw) were found in the deep dermis, whereas vessels developing increased vascular permeability after nerve stimulation (visualized with the supravital dye Monastral blue B, a macro-molecular tracer) were localized predominantly in the superficial dermis. By contrast, i.v. substance P, which also causes increased cutaneous vascular permeability, predominantly caused deeper vessels to leak. As analyzed by electron microscopy, the vessels that developed permeability in response to nerve stimulation, and were thereby stained with Monastral blue B, were found to be exclusively postcapillary venules. 2) Disodium cromoglycate (DSCG), a mast cell stabilizing compound, inhibited the cutaneous vascular permeability induced by intradermal injections of anti-IgE in a dose-dependent manner. By contrast, vascular permeability induced by ENS was not influenced by disodium cromoglycate treatment. 3) ENS and i.v. substance P both induced cutaneous vascular permeability in mast cell-deficient W/Wv mice, despite the fact that their skin contained only 4.7% of the mast cells present in their normal +/+ litter mates. The magnitude of ENS-induced vascular permeability responses in W/Wv mice were similar to control +/+ and BALB/c mice. This study supports our earlier observations suggesting that mast cell activation is not essential for the initial, vascular permeability phase of neurogenic inflammation in rodent skin.
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PMID:Neurogenic inflammation, vascular permeability, and mast cells. II. Additional evidence indicating that mast cells are not involved in neurogenic inflammation. 169 95

Nonadrenergic, noncholinergic (NANC) neural bronchoconstrictor responses in guinea pig airways are due to the release of tachykinins from sensory nerves. We have performed an in vitro study using electrical field stimulation (EFS; 40 V, 0.5 ms, 8 Hz for 20 s) in guinea pig bronchi to investigate the effect of nedocromil sodium (NS) on NANC bronchoconstrictor responses. NS inhibited NANC bronchoconstriction in bronchi in a concentration-dependent manner, with a maximum inhibition of 40 +/- 4% (p less than 0.001, n = 6) at 100 microM. Cromolyn sodium, however, produced only 9 +/- 8% inhibition at the same molar concentration (p less than 0.05). NS did not affect the contractile response to substance P, nor did it modulate the cholinergic bronchoconstrictor response to EFS in tracheal smooth muscle. These results indicate that NS may modulate the release of tachykinins from airway sensory nerves.
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PMID:Nedocromil sodium modulates nonadrenergic, noncholinergic bronchoconstrictor nerves in guinea pig airways in vitro. 170 90

1. Opioids have been shown to inhibit substance P (SP) release from primary afferent neurones (PAN). In addition, opioid receptors have been identified on PAN of the vagus nerves. Sodium cromoglycate (SCG) decreases the excitability of C-fibres in the lung of the dog in vivo. We have utilised a multi-superfusion system to investigate the effect of opioids and SCG on the release of SP from the rat trachea in vitro. 2. Pretreatment of newborn rats with capsaicin (50 mg kg-1 s.c. at day 1 and 2 of life) resulted in a 93.2 +/- 6.3% reduction in tracheal substance P-like immunoreactivity (SP-LI) content when determined by radioimmunoassay in the adult. 3. Exposure to isotonically elevated potassium concentrations (37-90 mM), capsaicin (100 nM-10 microM), and bradykinin (BK; 10nm-1 microM) but not des-Arg9-BK (1 microM) stimulated SP-LI release by a calcium-dependent mechanism. 4. SCG (1 microM and 100 microM) did not affect spontaneous, potassium (60 mM)- or BK (1 microM)-stimulated SP-LI release. 5. Morphine (0.1-100 microM) caused dose-related inhibition of potassium (60 mM)-stimulated SP-LI release with the greatest inhibition of 60.4 +/- 13.7% at 100 microM. The effect of morphine was not mimicked by the kappa-opioid receptor agonist, U50,488H (10 microM) or the delta-opioid receptor agonist, Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE). 6. The effect of morphine was totally abolished by prior and concomitant exposure to naloxone (100 nM) which had no effect on control release values. 7. We conclude that opioid receptors, predominantly of the MM-opioid receptor subtype, inhibit SP-LI release from PAN in the rat trachea and suggest that centrally inactive MM-opioid receptor agonists may have therapeutic potential in the treatment of asthma.
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PMID:Morphine, but not sodium cromoglycate, modulates the release of substance P from capsaicin-sensitive neurones in the rat trachea in vitro. 171 4

When rat mast cells loaded with fluorescent Ca2+ indicator Quin 2 were exposed to either compound 48/80 (0.1 micrograms/mL) or substance P (2 microM) at 37 degrees C for 30 seconds in a Ca-free medium, a marked increase of Quin 2 fluorescence was noticed, indicating that Ca2+ was released from the intracellular Ca store. The pixel values of the whole cell image were displayed in a three dimensional projection. When mast cells were exposed to 48/80, the fluorescent increase was reflected as an increase of height and spreading of the image. When 0.01 to 1 mM of db-cAMP was pretreated for five minutes, an increase of Quin 2 fluorescence was inhibited in a dose-dependent fashion. Theophylline pretreatment also showed a preventive effect at 1 to 5 mM. A marked inhibition of the Quin 2 signal was induced by pretreatment with 0.01 mM of terfenadine (63.4% inhibition) or ketotifen (26.6% inhibition). Disodium cromoglycate also showed a similar inhibitory effect. In the measurement of the order parameters of liposomes, the addition of either terfenadine or ketotifen into the lipids increased the parameter value, indicating they provide the membrane stabilizing action.
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PMID:Intracellular calcium release induced by histamine releasers and its inhibition by some antiallergic drugs. 242 49

The mammalian tachykinins substance P (SP) and neurokinin A (NKA) are known to be present in sensory airway nerves of animals and humans. We studied the effect of mammalian and nonmammalian tachykinins on the conducting airways of anesthetized, mechanically ventilated Fisher 344 rats. Dose-dependent increases in lung resistance and decreases in dynamic compliance occurred after the intravenous administration of eledoisin (E), kassinin (K), NKA, and SP. E, K, and NKA were more potent bronchoconstrictors than was SP. Neurokinin B (NKB) caused a similar decrease in dynamic compliance, but had no effect on lung resistance. This order of potency suggests a predominance of NK-2 receptors in the rat airways. Both atropine and the 5-hydroxytryptamine antagonist methysergide largely reduced the bronchoconstriction induced by E and SP. Vagotomy did not change this reaction, whereas pretreatment with the ganglion blocker hexamethonium slightly enhanced the bronchoconstrictor action of E and SP. Sodium cromoglycate and nedocromil sodium, 2 drugs that can inhibit mediator release from inflammatory cells, significantly reduced the bronchoconstrictor action of NKA. Ketotifen, an antihistamine with mast-cell-stabilizing properties, significantly reduced the bronchoconstriction induced by E, whereas the H1-receptor antagonist clemastine had no effect. We conclude that tachykinins cause bronchoconstriction in rats largely by an indirect mechanism, involving both acetylcholine and 5-hydroxytryptamine. We suggest that tachykinins cause bronchoconstriction by stimulation of postganglionic vagal nerve endings and mast cells.
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PMID:The mechanism of tachykinin-induced bronchoconstriction in the rat. 246 68

Rat peritoneal mast cells were exposed to the neurohormone and basic opioid peptide beta-endorphin. beta-Endorphin induced a dose-dependent release of histamine from the mast cells. A significant histamine release was found at 5 mumol/l of beta-endorphin and maximal release (35% of total) at 20 mumol/l. The histamine release process was very rapid and terminated within 30 s at 37 C, and in this sense is very similar to the histamine release induced by compound 48/80 or neurotensin. The histamine release was temperature-dependent showing an optimum release around 30 C, and it was independent of available extracellular calcium, but was inhibited in the presence of high extracellular calcium concentrations. Naloxone, only in very high concentrations (10 mmol/l), inhibited the release, and the very same concentration also inhibited the neurotensin - as well as the compound 48/80-induced histamine release. Cromoglycate and benzalkoniumchloride, a 48/80 antagonist, both produced a progressive dose-dependent inhibition of beta-endorphin-, neurotensin- as well as compound 48/80-induced histamine release. Taken together, the findings indicate that the opioid peptide beta-endorphin induces a selective, energy-dependent release of histamine from peritoneal rat mast cells. The pattern of release has much in common with that of compound 48/80 and other basic peptides, such as neurotensin and substance P. In addition this pattern of release is similar to that induced by dynorphin.
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PMID:Characteristics of beta-endorphin-induced histamine release from rat serosal mast cells. Comparison with neurotensin, dynorphin and compound 48/80. 246 22

To determine whether anti-allergic drugs can inhibit autonomic neurotransmission of airway smooth muscle, we studied the effect of sodium cromoglycate (SCG, Intal) and related anti-allergic drugs on electrically induced neurogenic contractions of isolated guinea pig bronchial muscle. Electrical field stimulation (8 Hz, 0.5 msec, 30 V) evoked a biphasic contraction of bronchial muscle, consisting of an initial phasic component followed by a sustained one which was mediated by cholinergic and non-cholinergic nerve stimulations, respectively. Sodium cromoglycate, tranilast, ketotifen, and azelastine at concentrations higher than 10(-6) M caused a concentration-dependent inhibition in the height of the non-cholinergically mediated contractions. The cholinergically mediated contractions were also inhibited by tranilast, ketotifen, and azelastine but not by SCG. Submaximal contractions of bronchial muscle evoked by exogenous substance P (2 X 10(-7) M) were less potently inhibited by these drugs than those by exogenous acetylcholine (2 X 10(-6) M). These results indicate that in isolated guinea pig bronchial muscle, anti-allergic drugs may inhibit non-cholinergic neurotransmission mainly by prejunctional reduction of the transmitter release and partly by postjunctional depression of the response.
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PMID:Inhibitory effect of anti-allergic drugs on cholinergic and non-cholinergic neurotransmissions of guinea pig bronchial muscle in vitro. 247 61

Neurotensin induced the release of histamine from both purified and non-purified rat peritoneal mast cells by a non-cytotoxic mechanism. It was effective at a concentration as low as 10(-8) M. The dose-response curve for the neurotensin effect was triphasic: and initial gentle rise, a plateau (2.5 X 10(-7) -2.5 X 10(-6) M) and a second rise. Disodium cromoglycate markedly, but benzalkonium chloride only slightly, inhibited the neurotensin-induced release. The effect of neurotensin was markedly different from that of substance P, bradykinin and compound 48/80 with respect to both the dose-response curve and the sensitivity to benzalkonium chloride. These inducers of histamine release showed somewhat different effects with changes in pH and temperature. Their actions did not require extracellular Ca2+. The results indicate that neurotensin is a potent histamine releaser acting directly on mast cells. Its mode of action may be different from those of the other substances tested.
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PMID:Histamine release induced by neurotensin from rat peritoneal mast cells. 617 50

A close anatomical relationship between nerves containing substance P and calcitonin gene-related peptide (CGRP) and mast cells containing serotonin has been demonstrated in the rat lacrimal gland. This study investigates the potential for peptidergic regulation of lacrimal mast cells by examining the actions of substance P, CGRP and serotonin on protein and peroxidase secretion from isolated lacrimal segments and on substance P and CGRP to release serotonin from the lacrimal mast cells. Substance P, CGRP and serotonin evoked marked increases in total protein and peroxidase from the lacrimal. Sodium cromoglycate, a mast cell stabilizer, significantly reduced or blocked the secretory responses elicited by these agonists. Chromatographic analysis using electrochemical detection revealed that substance P, but not CGRP, augmented the release of serotonin from the gland. The substance P evoked peroxidase secretion and serotonin release was blocked by CGRP and by sodium cromoglycate. These results support a role for mast cells in the regulation of lacrimal secretion and suggest a novel regulatory interaction between substance P and CGRP in the control of lacrimal function through a neuro-immune interaction.
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PMID:Secretion and serotonin release in the isolated rat lacrimal gland: the effects of substance P and calcitonin gene-related peptide. 891 52


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