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)

Substance P causes histamine release from rat peritoneal mast cells probably through direct activation of a specific G protein at micromolar concentrations. We found that peritoneal mast cells of a substrain of Wistar rats (Std:Wistar) responds to nanomolar concentrations of substance P by releasing histamine in a concentration-dependent manner. In addition, potent histamine release from peritoneal mast cells of the substrain rats was also induced by neurokinin A in a concentration-dependent fashion. Histamine release induced by low concentrations of substance P was significantly blocked by a tachykinin NK1 receptor antagonist, CP-96345 [(2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1-aza bicyclo[2.2.2]octan-3-amine dihydrochloride], whereas that induced by concentrations as high as 10 microM appeared resistant to the antagonist. The concentration-histamine release curve for neurokinin A was parallel-shifted to the right by the drug. A tachykinin NK2 receptor antagonist, SR-48968 [(S)-N-methyl-N[4-(4-acetylamino-4-phenyl piperadino)-2-(3,4-dichlorophenyl)butyl]benzamide], did not influence release stimulated by substance P and neurokinin A. On the other hand, peritoneal mast cells of Sprague-Dawley and other Wistar rats did not respond to neurokinin A. At over 1 microM but not at nanomolar concentrations, substance P caused modest histamine release from peritoneal mast cells of these rats. The results suggest that neurokinin A and nanomolar, but not micromolar concentrations of substance P stimulate tachykinin NK receptors on the peritoneal mast cells of Std:Wistar rat to release histamine.
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PMID:Nanomolar concentrations of neuropeptides induce histamine release from peritoneal mast cells of a substrain of Wistar rats. 1042 70

Neural mechanisms contribute to control of mucus secretion in the airways. Fenspiride is a non-steroidal antiinflammatory agent which has a variety of actions, including inhibition of neurogenic bronchoconstriction. The effect of fenspiride on neurally-mediated mucus secretion was investigated in vitro in electrically-stimulated ferret trachea, using(35)SO(4)as a mucus marker. Cholinergic secretory responses were isolated using adrenoceptor and tachykinin receptor antagonists. Tachykinin responses were isolated using cholinoceptor and adrenoceptor antagonists. Electrical stimulation increased cholinergic secretion by;90% and tachykininergic secretion by;40%. Fenspiride (1 microM-1 mM) tended to inhibit cholinergic secretion in a concentration-dependent manner, although only at 1 mM was inhibition (by 87%) significant. Inhibition by fenspiride of tachykininergic secretion was not concentration-dependent, and again significant inhibition (by 85%) was only at 1 mM. Inhibition was not due to loss of tissue viability, as assessed by restitution of secretory response after washout. Fenspiride also inhibited secretion induced by acetylcholine, but did not inhibit substance P-induced secretion. Histamine receptor antagonists increased basal secretion by 164%, whereas fenspiride did not affect basal secretion. We conclude that, in ferret trachea in vitro, fenspiride inhibits neurally-mediated mucus secretion, with antimuscarinic action the most plausible mechanism of action, but not necessarily the only mechanism.
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PMID:Effect of fenspiride, a non-steroidal antiinflammatory agent, on neurogenic mucus secretion in ferret trachea in vitro. 1058 77

Anti-scratch effects of oxatomide and epinastine were examined in mice. Scratching behavior and cutaneous reactions were induced in BALB/c, ICR and ddY mice by dinitrofluorobenzene painting, passive cutaneous anaphylaxis and substance P injection, respectively. Although oxatomide and epinastine failed to inhibit scratching behavior in BALB/c mice, they inhibited the cutaneous reaction significantly. The drugs potently inhibited both scratching behavior and cutaneous reaction in ICR mice. They also inhibited scratching behavior and cutaneous reaction in ddY mice, although cetirizine and terfenadine failed to affect them. Histamine did not induce frequent scratching behavior in BALB/c and ddY mice. These results indicate that oxatomide and epinastine inhibit the scratching behavior in ICR mice associated with passive cutaneous anaphylaxis mainly through an antagonistic action on histamine H(1) receptors. The results also indicate that these drugs inhibit substance P-induced scratching behavior in ddY mice through an action independent of the antagonistic action on histamine H(1) receptors.
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PMID:Evaluation of anti-scratch properties of oxatomide and epinastine in mice. 1091 87

The effects of histamine and the more selective H3 receptor agonist (R)alpha-methylhistamine were investigated on contractile responses produced by electrical stimulation of the longitudinal and circular muscles of the rat ileum and the circular muscle of the human colon. Histamine (0.1-3.0 microM) and (R)alpha-methylhistamine (0.1-3.0 microM) had no significant effect (P>0.05) on cholinergic nerve stimulation of either the longitudinal or circular muscle of the rat ileum nor the circular muscle of the human colon. Substance P (1 microM) and nicotine (0.1 microM), which both produce a contraction via activation of cholinergic nerves, were also unaffected by histamine (1 microM and 10 microM) or (R)alpha-methylhistamine (1 microM and 10 microM), in either tissue. Preliminary studies using in situ hybridisation histochemistry (ISHH) were performed in rat brain and ileum in an attempt to identify H3 receptor mRNA expression. This was done using 33P-labelled oligonucleotide-specific probes for rat H3 receptor mRNA. Unlike rat brain, where H3 receptor mRNA expression was found to be abundant in several regions, no H3 receptor mRNA expression could be detected in the rat ileum under the conditions used. These findings suggest H3 receptors have no role in the modulation of cholinergic neuronal function in the rat or human intestine unlike those in the guinea-pig. Furthermore, H3 receptors appear to be absent in the rat ileum.
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PMID:Lack of evidence for histamine H3 receptor function in rat ileum and human colon. 1121 65

Scratching behavior was induced in 12 strains of mice and the frequency was compared. An injection of histamine at a dose of 50 nmol induced frequent scratching behavior only in ICR mice, although the same dose of serotonin induced frequent scratching behavior in all strains of mice except for A/J. Histamine (10 nmol), serotonin (1 nmol), substance P (50 nmol) and passive cutaneous anaphylaxis induced significant vascular permeability increase in BALB/c, ICR, ddY and NC/Nga mice. These four stimuli also induced frequent scratching behavior in ICR mice. However, they failed to induce substantial increase in the incidence of scratching in the other three strains, except for ddY, which exhibited a slight but significant increase against substance P injection. These results suggest that the ICR mouse is a good responder for scratching behavior against various stimuli, especially against histamine. Thus ICR mice may be suitable for studying mediators and/or mechanisms for itching.
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PMID:Scratching behavior in various strains of mice. 1131 67

Substance P is located in cutaneous nerve fibres and induces wheal and flare responses, accompanied by granulocyte infiltration, upon intradermal injection. Studies with animal skin and rat peritoneal mast cells have suggested that substance P induces the release of histamine and leukotriene B4 (LTB4), a potent chemoattractant for granulocytes, from skin mast cells. However, the release of LTB4 has not been detected from mast cells enzymatically isolated from human skin. In order to investigate the mechanism of granulocyte infiltration induced by substance P in human skin, we studied the release of LTB4 and histamine in response to substance P, and the effect of dexamethasone using human skin obtained from 22 nonallergic individuals. Histamine was released from all skin tissue samples in a dose-dependent manner. However, the amount of LTB4 release, both constitutive and inducible, was variable among skin preparations. Substance P induced a large release of LTB4 from the skin of eight donors (twice to six times that of the spontaneous release), but no or only negligible release from the skin of 14 donors. The amount of constitutive release of LTB4 correlated with the amount of tissue histamine. Dexamethasone selectively abolished the inducible release of LTB4, without an effect on histamine release and the constitutive release of LTB4. These results suggest that substance P induces the release of LTB4 in a certain population of human individuals by a glucocorticosteroid-dependent mechanism, and plays an important role in neurogenic inflammation with granulocyte infiltration.
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PMID:The release of leukotriene B4 from human skin in response to substance P: evidence for the functional heterogeneity of human skin mast cells among individuals. 1135 54

We have compared the reactivity to spasmogens of longitudinal muscularis mucosae isolated from the human, guinea pig and rat colon in vitro. The muscularis mucosae isolated from the human distal colon responded with a sustained contractions to carbachol (10 nM-30 microM), in a concentration-dependent manner, and the maximum contraction was comparable to that with high potassium concentration (100 mM). Among several spasmogens, neurokinin A was the most potent with the following order of potency: carbachol, prostaglandin F2alpha and acetylcholine. Histamine, 5-hydroxytryptamine and bradykinin did not produce a recognizable contraction of this tissue. The muscularis mucosae isolated from the guinea pig distal colon demonstrated a concentration-dependent contraction in response to neurokinin A, carbachol, histamine and acetylcholine, but not to prostaglandin F2alpha or 5-hydroxytryptamine, and the maximum contraction was obtained with histamine. The muscularis mucosae from the rat distal colon was very sensitive to neurokinin A and bradykinin, less to carbachol and acetylcholine, and not at all sensitive to histamine, 5-hydroxytryptamine and prostaglandin F2alpha. It is concluded that the colonic muscularis mucosae respond to pharmacological agents in a species-different manner.
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PMID:Comparison of motor reactivity of the colonic muscularis mucosae isolated from human, guinea pig and rat in vitro. 1239 58

Intrathecal injection of histamine elicited a behavioral response consisting of scratching, biting and licking in conscious mice. Here, we have examined the involvement of substance P (SP) by using intrathecal injection of tachykinin neurokinin (NK)(1) receptor antagonists and SP antiserum. Histamine-induced behavioral response was evoked significantly 5-10 min after intrathecal injection and reached a maximum at 10-15 min. Dose-dependency of the induced response showed a bell-shaped pattern from 200 to 3200 pmol, and maximum effect was observed at 800-1000 pmol. The H(1) receptor antagonist, d-chlorpheniramine and pyrilamine but not the H(2) receptor antagonists, ranitidine and zolantidine, inhibited histamine-induced behavioral response. The NK(1) receptor antagonists, CP-99,994, RP-67580 and sendide, inhibited histamine-induced behavioral response in a dose-dependent manner. A significant antagonistic effect of [D-Phe(7), D-His(9)]SP (6-11), a selective antagonist for SP receptors, was observed against histamine-induced response. The NK(2) receptor antagonist, MEN-10376, had no effect on the response elicited by histamine. Pretreatment with SP antiserum resulted in a significant reduction of the response to histamine. No significant reduction of histamine-induced response was detected in mice pretreated with NK A antiserum. The present results suggest that elicitation of scratching, biting and licking behavior induced by intrathecal injection of histamine may be largely mediated by NK(1) receptors via H(1) receptors in the spinal cord.
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PMID:Intrathecal histamine induces spinally mediated behavioral responses through tachykinin NK1 receptors. 1247 71

We examined whether azelastine would inhibit itch-associated responses of mice to mosquito allergy. Repeated injections of mosquito salivary gland extract increased scratching and sensory nerve activity. Azelastine inhibited the increased scratching and nerve activity, while terfenadine was without effects. Dexamethasone did not affect the increased scratching. Azelastine suppressed high K(+)-induced increase in intracellular free Ca(2+) in primary cultures of mouse sensory neurons. Direct inhibition by azelastine of sensory neurons may be at least involved in the anti-pruritic effect of azelastine. Histamine, substance P, and leukotriene B(4) may not play a key role in the itching of mosquito allergy.
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PMID:Inhibitory effect of azelastine on allergic itch-associated response in mice sensitized with mosquito salivary glands extract. 1268 51

The participation of histamine H(3) receptors in the regulation of skin vascular permeability changes in mast cell-deficient mice was studied. Although intradermal injection of histamine H(3) antagonists, iodophenpropit and clobenpropit, at a dose of 100 nmol/site caused significant increases in skin vascular permeability in both mast cell-deficient (WBB6F1 W/W(v)) and wild-type (WBB6F1 +/+) mice, this response was significantly lower in mast cell-deficient mice than in the wild-type controls. Histamine also caused dose-related increases in skin vascular permeability in both wild-type and mast cell-deficient mice. Significant effects were observed at doses of 10 and 100 nmol/site, and no significant difference in skin vascular permeability was observed between mast cell-deficient and wild-type mice. However, histamine contents of dorsal skin in mast cell-deficient mice were significantly lower than in wild-type mice. In addition, the H(1) antagonists diphenhydramine and chlorpheniramine and the NK(1) antagonists, L-732,138 and L-733,060, were able to antagonize H(3) antagonist-induced skin vascular permeability. These results indicated that blockade of H(3) receptors by H(3) antagonists induce skin vascular permeability through mast cell-dependent mechanisms. In addition, histamine and, to a lesser extent substance P are involved in the reaction.
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PMID:Histamine H3 receptors regulate vascular permeability changes in the skin of mast cell-deficient mice. 1455 81


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