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 effect of prednisolone on the substance P (SP)-induced vascular permeability increase in male ddY, WBB6 F1(-)+/+ (control) and WBB6 F1-W/WV (no mast cell in skin or internal organs) mice was investigated. 1) SP (1-10,000 pg/site) increased vascular permeability in ddY, WBB6 F1(-)+/+ and WBB6 F1-W/WV mice ears. 2) SP (100 pg/site)-induced vascular permeability was inhibited by prednisolone (10 mg/kg) administered intraperitoneally 3 to 12 hours prior to the elicitation of the reaction in ddY mice. When dexamethasone at a dose of 1 mg/kg was administered intraperitoneally 2 to 24 hours prior to the elicitation of the reaction, significant inhibition was observed. When prednisolone was administered intraperitoneally 8 hours prior to the elicitation of the reaction, the SP-induced capillary permeability increase in both ddY and WBB6 F1-W/WV mice was clearly inhibited by the drug at doses of 5 and 10 mg/kg. 3) Diphenhydramine (1 and 10 mg/kg) inhibited SP-induced vascular reaction in ddY mice but not in WBB6 F1-W/WV mice. 4) Atropine (10 mg/kg) inhibited SP-induced vascular reaction in both ddY and WBB6 F1-W/WV mice. But acetylcholine did not cause an increase of vascular permeability in ddY and WBB6 F1-W/WV mice ears. 5) Prednisolone (5 mg/kg) inhibited histamine- and serotonin-induced vascular permeability in ddY and WBB6 F1-W/WV mice ears. 6) Prednisolone (5 and 10 mg/kg) inhibited the SP-induced histamine release from ddY mice peritoneal mast cells. These results suggest that the vascular effect of SP is mediated by both mast cell dependent (release of histamine from mast cells) and mast cell independent mechanisms. Prednisolone inhibits the SP-induced vascular permeability mediated by both mechanisms in mice.
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PMID:The effect of prednisolone on substance P-induced vascular permeability in mice. 138 66

1. The effect of systemic administration of ruthenium red on bronchospasm induced by acetylcholine, capsaicin or selective tachykinin receptor agonists ([Sar9]SP sulfone or [beta Ala8]-neurokinin A (NKA)-(4-10) for NK-1 and NK-2 receptors, respectively) was studied in anaesthetized guinea-pigs. 2. The bronchospasm induced by capsaicin was reduced by ruthenium red, which did not affect the response induced by acetylcholine. Atropine, which totally blocked the response to acetylcholine, also partially blocked the bronchospasm induced by capsaicin. 3. The inhibitory action of atropine and ruthenium red on the bronchospasm produced by capsaicin was additive, independently from the order of administration of the two antagonists. 4. Ruthenium red induced an increase in [Sar9]SP sulfone-bronchospasm and a marked enhancement of the bronchomotor response to [beta Ala8]NKA-(4-10). This latter was antagonized by the prior administration of the selective NK-2 receptor antagonist MEN 10,376. 5. Pretreatment with guanethidine or propranolol increased the airway constriction induced by [beta Ala8]NKA-(4-10). Furthermore, pretreatment with guanethidine prevented the enhancement induced by ruthenium red, showing that activation of NK-2 receptors influences the sympathetic bronchodilator drive to the airways. 6. It is concluded that ruthenium red antagonizes selectively the in vivo excitatory effect of capsaicin in guinea-pig airways. Furthermore, the additivity of the blocking action of ruthenium red and atropine indicates that two distinct mechanisms take place in bronchospastic response to i.v. capsaicin in this species.
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PMID:Effect of ruthenium red on the bronchoconstriction induced by capsaicin and by selective tachykinin receptor agonists in anaesthetized guinea-pig. 138 38

1. Interactions between pulmonary cholinergic and noradrenergic nerves were studied in the innervated tracheal tube preparation isolated from guinea-pigs anaesthetized with urethane. Relaxations of the trachealis smooth muscle in response to postganglionic stimulation of the sympathetic nerve were recorded as decreases in the intraluminal pressure of the tracheal tube after the pressure had been raised with the stable thromboxane-mimetic, U46619. In contrast, contractions following preganglionic stimulation of the vagal nerve trunk were recorded as increases in intraluminal pressure. 2. In approximately half of the preparations studied, concurrent stimulation of of the vagal nerve trunk the vagal nerve trunk inhibited relaxation responses elicited by stimulation of the sympathetic nerves. The vagi were stimulated at parameters which caused no change in intraluminal pressure, excluding the involvement of postjunctional mechanisms. 3. The effect of simultaneous stimulation of the sympathetic nerve trunk was studied on contractile responses evoked by preganglionic stimulation of the vagus nerve. In 80% of the preparations tested the vagal responses were inhibited. This inhibitory effect of sympathetic nerve stimulation was antagonized by propranolol. 4. The potassium channel agonist, cromakalim, endothelins 1 and 3 and the neuropeptides, vasoactive intestinal peptide, neurokinin A and substance P, did not significantly modulate sympathetic nerve-induced relaxations. 5. The anticholinesterase drug, physostigmine, induced a concentration-dependent increase in the intraluminal pressure of the tracheal tube and potentiated the postjunctional action of exogenously applied acetylcholine to contract the guinea-pig trachealis muscle. In the presence of higher concentrations of physostigmine both vagally-induced contractions and sympathetic nerve-induced relaxations were reduced. Atropine blocked both the inhibitory effect of physostigmine on sympathetic relaxations and its postjunctional contractile action on the trachealis smooth muscle.6. It is concluded that, in the guinea-pig trachea, acetylcholine released endogenously from pulmonary parasympathetic nerves, either by anticholinesterase drugs or in response to nerve stimulation, can inhibit transmission in the adjacent sympathetic nerves via activation of prejunctional muscarinic heteroreceptors, probably of the M3 subtype.
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PMID:Evidence for inhibition of sympathetic neurotransmission by endogenously released acetylcholine in the guinea-pig trachea. 166 87

(1) Circularly-oriented muscle strips from the human ileum responded to electrical field stimulation (1-50 Hz) with frequency-related primary relaxation at low frequency and primary contractions at high frequencies of stimulation. Both responses were abolished or markedly reduced by tetrodotoxin (1 microM). (2) Atropine (3 microM) or omega conotoxin (0.1 microM) reduced but dit not abolish contraction to electrical field stimulation and enhanced the relaxation. Omega conotoxin (0.1 microM) did not affect carbachol-induced contraction nor isoprenaline-induced relaxation. (3) Neurokinin A and substance P (1 nM-1 microM) produced a concentration-dependent contraction. The NK-1 receptor selective agonist, [Pro9]SP sulfone and the NK-2 receptor selective agonist [beta Ala8]NKA(4-10) produced a contraction superimposable to that of substance P and neurokinin A, respectively. On the other hand, [MePhe7]-neurokinin B, an NK-3 receptor selective agonist was ineffective up to 1 microM. The response to substance P or neurokinin A was unaffected by atropine (3 microM). (4) Galanin, up to 0.1 microM, produced a weak and inconsistent contraction. (5) Vasoactive intestinal polypeptide (10 nM-1 microM) produced a concentration-dependent relaxation while human alpha calcitonin gene-related peptide exerted a weak and inconsistent relaxant effect. (6) These findings indicate that both cholinergic excitatory and non-cholinergic inhibitory nerves affect the motility of the circular muscle of the human small intestine. Transmitter release from excitatory nerves seems largely mediated by activation of omega conotoxin-sensitive (N-type) calcium channels. Tachykinins exert a potent contractile effect, independently of cholinergic nerves, via NK-1 and NK-2 receptors.
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PMID:Human isolated ileum: motor responses of the circular muscle to electrical field stimulation and exogenous neuropeptides. 169 76

We measured the intracellular free calcium ion concentration [( Ca2+]i) of acinar cells in isolated feline tracheal submucosal glands in response to secretagogues using the Ca2(+)-sensitive fluorescent dye fura-2. The secretagogues included cholinergic, adrenergic agonists, substance P (SP), and vasoactive intestinal polypeptide (VIP) which induce mucus glycoprotein secretion from feline tracheal submucosal glands. Methacholine (MCh) produced a significant increase in [Ca2+]i of up to 9.8 times that of control in a dose-dependent fashion at concentrations of 10(-8) to 10(-3) M. [Ca2+]i increase by MCh reached a peak within 30 s after stimulation and thereafter showed a sustained rise. In Ca2(+)-free medium, MCh produced an initial transient rise, which was less than 30% of that in a Ca2(+)-containing solution, and which lasted for 60 s with no prolonged sustained rise in [Ca2+]i. Atropine abolished MCh-evoked [Ca2+]i increase. Phenylephrine and SP produced a prolonged increase in [Ca2+]i without an initial transient increase. Phenylephrine (up to 10(-4) M) evoked an increase in [Ca2+]i by up to 240% that of control, which was abolished by prazosin. SP (up to 10(-4) M) also evoked an increase in [Ca2+]i by 155% that of control, which was abolished by atropine. By contrast, both isoproterenol (up to 10(-5) M) and VIP (up to 10(-5) M) failed to alter [Ca2+]i. These findings indicate that the mucus glycoprotein secretion evoked by muscarinic cholinergic, alpha-adrenergic agonist or SP can be mediated by intracellular Ca2+, whereas that by beta-adrenergic agonists or VIP cannot.
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PMID:Intracellular calcium concentration of acinar cells in feline tracheal submucosal glands. 170 76

The interaction between bombesin and acetylcholine acting on smooth muscle of the stomach wall was investigated in two species of teleost fish. Oncorhynchus mykiss (rainbow trout) and Gadus morhua (Atlantic cod). Acetylcholine or bombesin alone has an excitatory effect on the stomach muscle. The effect on contraction amplitude of acetylcholine (10(-6)-10(-5) M) alone is about 10-times greater than the effect of bombesin (10(-9)-10(-7) M). In molar terms however, bombesin is more potent than acetylcholine. Bombesin (10(-8)-10(-7) M) added 0.5-3 min prior to acetylcholine potentiates the effect of acetylcholine in a dose-dependent manner. The potentiation is most pronounced in circular muscle preparations, but is present also in longitudinal muscle preparations. Bombesin affects the response to carbachol (10(-6) M) with a similar potentiation, indicating that the potentiation is not caused by inhibition of choline esterase activity. Atropine (10(-6)-10(-5) M) abolishes the response to bombesin plus acetylcholine as well as the response to acetylcholine alone. Tetrodotoxin (10(-6) M) does not block the effect of acetylcholine, bombesin or the combination acetylcholine plus bombesin. Substance P (10(-9)-10(-7) M) which has a similar excitatory effect on the stomach muscle as bombesin, does not potentiate the effect of acetylcholine. Immunohistochemistry has shown the presence of strong bombesin-like immunoreactivity in stomach nerves of the cod and weak bombesin-like immunoreactivity in rainbow trout nerves. In addition, bombesin-like immunoreactivity was demonstrated in endocrine cells in the gastric and intestinal mucosa of both species. It is concluded that bombesin, contained either in nerve fibres or in mucosal endocrine cells, specifically potentiates the effect of acetylcholine in the fish stomach.
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PMID:Bombesin potentiates the effect of acetylcholine on isolated strips of fish stomach. 170 14

The effects of inhaled bradykinin (BK), substance P (SP), and neurokinin A (NKA) on pulmonary resistance and airway responsiveness to carbachol were studied in conscious allergic sheep. Inhaled BK (20 breaths, 0.1 to 5.0 mg.ml-1) caused dose-dependent increases in pulmonary resistance. Neither inhaled SP nor NKA (20 breaths, 0.1 to 1.0 mg.ml-1) produced significant bronchoconstriction in allergic sheep. However, the response to SP could be enhanced (p less than 0.05) by pretreatment with the neutral endopeptidase inhibitor, thiorphan (40 breaths, 1 mg.ml-1). Sheep that were allergic to Ascaris suum antigen were 5.9 times (p less than 0.05) more sensitive to the constrictor effects of BK than nonallergic sheep. BK-induced bronchoconstriction was blocked in a dose-dependent fashion by the BK beta 2-receptor antagonist, NPC 567 (D-arginine[hydroxyproline3,D-phenylalanine7]BK). Atropine (0.2 mg.kg-1, intravenously) and nedocromil sodium (1 mg.kg-1 in 3 ml of saline, aerosolized) significantly inhibited the BK-induced bronchoconstriction by 97% and 43%, respectively. Chlorpheniramine (2 mg.kg-1, intravenously) had no effect. NKA caused a transient increase in airway responsiveness in allergic sheep, producing a mean 1.9-fold leftward shift in dose-response curves to aerosolized carbachol (p less than 0.05). This hyperresponsiveness was not evident 24 hours after NKA challenge. Neither SP nor BK changed airway responsiveness. Thus, in allergic sheep, inhaled BK caused a more pronounced bronchoconstriction than that observed in nonallergic sheep. The bronchoconstriction was blocked by a BK-receptor antagonist and appeared to be partially mediated via cholinergic reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Airway effects of inhaled bradykinin, substance P, and neurokinin A in sheep. 170 88

We studied the role of gastrin-releasing peptide (GRP) for porcine gallbladder motility. Immunohistochemistry visualized nerve fibers containing GRP-like immunoreactivity in muscularis. GRP concentration dependently stimulated contractions of muscularis strips (ED50, 2.9 nM). Neuromedin B was less potent (ED50, 0.1 microM), suggesting existence of GRP-preferring receptors. GRP-induced contractions were unaffected by muscarinic antagonism (1 microM atropine), axonal blockade (1 microM tetrodotoxin), cholecystokinin (CCK) receptor antagonism (10 microM MK-329), or substance P desensitization (1 microM), supporting the existence of myogenic GRP receptors. The bombesin (BN) analogue D-Phe6-BN-(6-13)propylamide (PA) stimulated contractions (ED50, 3.3 nM) with low efficacy (29% of that of GRP). D-Phe6-BN-(6-13)PA (1 microM) shifted GRP concentration-response curves one log to the right. D-Phe6-BN-(6-13)PA interacted specifically with GRP receptors; while abolishing responses to GRP (1 nM), responses to substance P (0.1 microM) and CCK-8 (1 nM) were unchanged. Electrical stimulation (10 Hz, 0.5 ms, 10 V) caused a rapid onset-slow offset, tetrodotoxin-sensitive excitation. Atropine reduced the amplitude to 58% and caused a delayed, slow onset-slow decline response. D-Phe6-BN-(6-13)PA reduced the amplitude to 59% and caused a very rapid onset-rapid decline response. Atropine plus D-Phe6-BN-(6-13)PA abolished responses to nerve stimulation. Nerve stimulation caused significant release of GRP-like immunoreactivity. Thus two neural inputs were defined: a cholinergic rapid onset-rapid offset excitation and a delayed, slow onset-slow offset excitation caused by release and subsequent binding of GRP to GRP-preferring receptors.
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PMID:Gastrin-releasing peptide is a transmitter mediating porcine gallbladder contraction. 170 7

1. Contractile responses and acetylcholine release evoked by nicotine in guinea-pig detrusor strips were determined by isotonic transducer and radioimmunoassay, respectively. Nicotine stimulated acetylcholine release and a contractile response in guinea-pig detrusor strips treated with the cholinesterase inhibitor, methanesulphonyl fluoride (MSF). Both actions evoked by nicotine were antagonized by the nicotinic receptor antagonist, hexamethonium but were insensitive to tetrodotoxin. 2. A sympathetic nerve blocker, guanethidine and a tachykinin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP) partially inhibited the acetylcholine release evoked by nicotine to much the same degree. The inhibitory effects of guanethidine and rpwwL-SP on acetylcholine release were significantly greater than corresponding effects on the contraction evoked by nicotine. 3. In preparations treated with rpwwL-SP to block the tachykinin receptors, guanethidine had no effect on the response to nicotine. Conversely, after treatment with guanethidine to block release of a mediator from sympathetic nerve endings, nicotine-induced responses were not affected by rpwwL-SP. 4. Nicotine-induced contraction was reduced to 30% by the muscarinic cholinoceptor antagonist, atropine and completely abolished after desensitization of P2-purinoceptors with alpha,beta-methylene ATP in the presence of atropine. 5. A concentration-contractile response curve to neurokinin A (NKA) was shifted to the left after cholinesterase inhibition with MSF. Atropine abolished the facilitatory effect of MSF and partially inhibited contractions induced by NKA at 100 nM to 1 microM. The contractile responses to substance P methyl ester (SPOMe) and Tyr0-neurokinin B (Tyr0-NKB) were not influenced by MSF or atropine. 6. After desensitization of NK, tachykinin receptors with SPOMe or preincubation with senktide, the cholinergic component of the nicotine-induced contraction was the same as the control value (100%). 7. Our findings give further support to our previous results: nicotine stimulates acetylcholine release in a tetrodotoxin-resistant manner in guinea-pig bladder and acetylcholine release evoked by nicotine is increased by the coordinated action of sympathetic nerves and tachykinin(s). It is suggested that the tachykinin receptor subtype involved in acetylcholine release is NK,.
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PMID:Contrasting effects of tachykinins and guanethidine on the acetylcholine output stimulated by nicotine from guinea-pig bladder [corrected]. 171 27

Electrical stimulation of the right vagus nerve causes a biphasic contraction of the guinea pig isolated right bronchus. The "first-phase" is blocked by hexamethonium or atropine and the "second-phase" is eliminated by capsaicin pretreatment. We investigated a potential interaction between capsaicin-sensitive nerves and cholinergic nerves in the guinea pig bronchus. Hexamethonium (100 microM) abolished the first-phase contraction but had no effect on the capsaicin-sensitive second-phase contraction. In the presence of hexamethonium, atropine (0.1 microM) significantly decreased the amplitude of the second-phase contraction by 28%. Similar results were observed with the M3-selective muscarinic receptor antagonist, 4-diphenyl-acetoxy-M-methylpipe-radine, but not with the M2 muscarinic antagonist, AFDX-116. Atropine also reduced contractions induced by exogenously applied neurokinin A. We then analyzed the effect of stimulating capsaicin-sensitive fibers with electrical field stimulation on vagus nerve evoked cholinergic contractions. By reducing the stimulus intensity we were able to evoke vagus nerve-mediated contractions that were exclusively cholinergic in nature. The cholinergic contractions were significantly increased after stimulation of capsaicin-sensitive fibers by about 50%. By contrast, contractions elicited by exogenous methacholine were unaffected after field stimulation of capsaicin-sensitive responses. Our findings indicate that the contractions of the guinea pig bronchus elicited by stimulation of capsaicin-sensitive nerves are due in part to muscarinic cholinergic receptor activation. Secondly, our data demonstrate that the cholinergic contractions elicited by vagal preganglionic nerve stimulation are potentiated by neurotransmitter(s) released from capsaicin-sensitive fibers in bronchus.
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PMID:Functional interactions between capsaicin-sensitive and cholinergic nerves in the guinea pig bronchus. 171 77


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