Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the serial changes of intravenously applied dye leakage and preliminary examined histamine release into nasal lavage fluid after topical stimulation with capsaicin in guinea pigs. A significant increase in the dye leakage response was detected for 30-40 min, with the maximum response occurring between 5 and 10 min after topical capsaicin stimulation. The dye leakage response to nasal capsaicin challenge was abolished by pretreatment with topical lidocaine, general substance P analogue, topical or general high dosage capsaicin. The dye leakage response to topical capsaicin challenge was significantly reduced following pretreatment with antihistamine, diphenhydramine or atropine sulfate, although it was not affected by pretreatment with an anti-leukotriene, FPL 55712. Topical methacholine challenge did not induce a dye leakage response. An increase in the concentration of histamine in the nasal lavage fluid was noted at 5 min after topical capsaicin challenge. The concentrations of released histamine tended to be positively correlated with those of leaked dye in the nasal lavage fluids. The histamine release induced by topical stimulation with capsaicin tended to be reduced following general and topical pretreatments with high dosage of capsaicin, and was almost completely abolished following atropine pretreatment. From this study it was concluded that nasal capsaicin stimulation can reflexively induce an intravenously applied dye leakage into the nasal cavity, and that C-fiber related cholinergic nerve reflex and histamine release might, at least partially, be related to this response.
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PMID:Study on the dye leakage response of nasal mucosa following topical, capsaicin challenge in guinea pigs. 127 30

We examined the effects of novel tachykinin antagonists, FR 113680 (N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-phenylmethyl-L-phenylalaninamide) and FK 224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N[3-(2-phenthylpheny l) - propionyl]-L-threonyl]-tyrosyl]-L-leucynyl]-D-phenylalanyl]-L-allo - threonyl]-L-asparaginyl]-L-serine nu-lactone) on rat tracheal plasma extravasation induced by cigarette smoke. Intravenous injection of FK 224 (0.032-3.2 mg kg-1) inhibited rat tracheal plasma extravasation induced by cigarette smoke and capsaicin. FR 113680 (32 mg kg-1 i.v.) also significantly inhibited cigarette smoke-induced plasma extravasation, whereas D-chlorpheniramine maleate, FPL 55712, atropine sulfate and indomethacin had no effect. Tracheal plasma extravasation induced by substance P (SP) and neurokinin A (NKA), but not histamine, was also reduced by intravenous administration of FR 113680 and FK 224. These findings suggest that cigarette smoke stimulates primary afferent sensory nerves, releases tachykinins and evokes plasma extravasation in rat trachea.
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PMID:Effects of FR 113680 and FK 224, novel tachykinin receptor antagonists, on cigarette smoke-induced rat tracheal plasma extravasation. 128 May 94

1. Intravenous administration of substance P (SP) or of the NK1 selective agonist [beta-Ala4, Sar9, Met (O2)11] SP-(4-11) increased vascular permeability in the urinary bladder of urethane-anaesthetized rats, providing evidence for an NK1 receptor-mediated inflammatory response. 2. BW 755C, a dual inhibitor of arachidonate cyclo-oxygenase and lipoxygenase, significantly reduced the plasma extravasation induced by SP, but did not modify the effect of [beta-Ala4, Sar9, Met (O2)11] SP-(4-11). 3. SP-induced microvascular leakage was also inhibited by systemic pretreatment with indomethacin or with the prostaglandin receptor antagonist SC-19220, while it was unaffected by the selective 5-lipoxygenase inhibitor BW A4C or the leukotriene antagonist FPL 55712. 4. Pretreatment of rats with the mast cell degranulating agent compound 48/80 significantly attenuated the inflammatory effect of SP. Indomethacin administration to 48/80-pretreated animals failed to produce further inhibition. 5. These findings indicate that intravascular SP promotes plasma exudation in rat urinary bladder through an NK1-mediated effect on venular permeability and the release of cyclo-oxygenase metabolites of arachidonic acid. The latter effect largely derives from the interaction of the neuropeptide with mast cells.
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PMID:Microvascular leakage induced by substance P in rat urinary bladder: involvement of cyclo-oxygenase metabolites of arachidonic acid. 138 Sep 64

Although certain prostaglandins have been found to be inhibitory to nerve-evoked salivary flow, little is known of the effects the leukotrienes on salivary secretion. It was the purpose of this investigation to examine the effects of leukotrienes C4 (LTC4) and D4 (LTD4) on salivary secretion in the rat, using methacholine or substance P to induce basal secretion, and to test whether or not the observed effects of these eicosanoids were receptor-mediated by using the leukotriene receptor blocker FPL-55712. Methacholine (3 x 10(-4) M), or substance P (1 x 10(-6) M) was infused intra-arterially to stimulate secretion and saliva was collected separately from the parotid gland and the submandibular gland of anesthetized rats. LTC4 and LTD4 (each at 1 x 10(-9) to 1 x 10(-6) M) were found to reduce methacholine- and substance P-induced salivary flow in a dose-related manner. Salivary protein concentration and amylase activity were not significantly altered by the leukotrienes; however, arginine-esterase activity, stimulated by substance P, was increased by both leukotrienes. FPL-55712 (1 x 10(-8) M) was shown to reduce the inhibitory effects of LTC4 and LTD4, suggesting the involvement of leukotriene receptors for these agents in their action.
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PMID:The modulatory effects of leukotrienes C4 and D4 on methacholine- and substance P-induced salivary secretion in rats. 245 57

Formylmethionylleucylphenylalanine (FMLP) is a synthetic analogue of bacterial chemotactic factors. We studied the contraction of human airway tissue in vitro by FMLP. FMLP induced a concentration-dependent contraction of all bronchial spiral strips studied (n = 45). The maximum tension generated in response to FMLP was 86.6 +/- 7.0% (SE) of the maximum response to histamine. The contraction was not reduced by the histamine H1-receptor antagonist pyrilamine, the cyclooxygenase and lipoxygenase inhibitors indomethacin and BW755C, the muscarinic antagonist atropine, or capsaicin which depletes stores of substance P. The concentration-response curve was shifted to the right by the polypeptide antagonist N-t-BOC-phenylalanylleucylphenylalanylleucylphenylalanine and the leukotriene antagonist FPL 55712. When 2 successive FMLP concentration-response curves were performed the maximum response was significantly reduced from 114.8 +/- 9.1% of the histamine maximum to 39.3 +/- 6.1%. The contraction of human airways in vitro by an agent that is structurally and functionally similar to chemotactic peptides released from bacteria may have important implications in airway disease.
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PMID:Formyl peptide-induced contraction of human airways in vitro. 394 25

To examine endogenous factors affecting the development of the massive bronchoconstriction in the postmortem guinea pig lung, 58 anesthetized open-chest animals were divided into three groups: 1) exsanguination only (n = 13), 2) pulmonary perfusion with 5% dextran and 1% bovine serum albumin (BSA) in Tyrode's solution (Ca2+ perfusate) (n = 21), and 3) pulmonary perfusion with 5% dextran and 1% BSA in saline (Ca2+-free perfusate) (n = 24). These groups were further divided into several subgroups according to treatments: 1) substance P depletion by chronic administration of capsaicin, 2) acute capsaicin treatment to release substance P, 3) dazoxiben treatment to block endogenous synthesis of thromboxane A2, 4) diethylcarbamazine treatment to eliminate leukotriene (LT) synthesis, and 5) FPL 55712 treatment to antagonize actions of LT. Vital capacity from the deflation pressure-volume (PV) curve of the lung was used as the indicator of bronchoconstriction. Most PV curves were performed for 30 min following exsanguination or artificial perfusion. Ca2+-free perfusate enhanced the airway spasm at 5-10 min, but the spasm disappeared gradually after 10 min. Substance P depletion significantly decreased (P less than 0.01) the bronchial constriction at 20-30 min, whereas substance P release induced severe airway spasm (P less than 0.01) during the entire study. In addition, FPL 55712 reduced the bronchospasm (P less than 0.05) in Ca2+ perfusate at 30 min. Thus Ca2+ and several endogenous mediators may be involved with the airway spasm of the postmortem guinea pig lung.
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PMID:Factors affecting massive postmortem bronchoconstriction in guinea pig lungs. 620 78

The present study was performed to investigate the mechanism underlying the acid stimulatory response in the stomach after damage under the inhibition of nitric oxide (NO) production by N(G)-nitro-L-arginine methyl ester (L-NAME). A rat stomach was mounted in an ex vivo chamber, perfused with saline, and the potential difference (PD) and acid secretion were measured before and after the application of 20 mM taurocholate (TC) for 30 min. Exposure of the stomach to TC caused a PD reduction and a decrease of acid secretion. Pretreatment with L-NAME did not affect basal acid secretion but significantly enhanced the acid secretion in the stomach after damage with TC, without any effect on the PD response. This effect of L-NAME was antagonized by simultaneous administration of L-arginine but not D-arginine. The luminal appearance of NO was significantly increased in the stomach after exposure to TC, and this change was completely blocked in the presence of L-NAME or when EGTA was applied together with TC. The enhanced acid secretory response to TC in the presence of L-NAME was inhibited by pretreatment with cimetidine, FPL-52694 (a mast cell stabilizer), or spantide (a substance P antagonist) or by chemical ablation of capsaicin-sensitive sensory neurons. Mucosal exposure to TC increased histamine output in the lumen and decreased the number of metachromatically staining cells in the stomach, and these changes were also significantly prevented by FPL-52694, spantide, or sensory deafferentation. These results suggest that 1) damage in the stomach may activate the acid stimulatory pathway in addition to the NO-dependent inhibitory mechanism, but the latter effect overcomes the former, resulting in a decrease in acid secretion, 2) the acid stimulation in the damaged stomach may be mediated by histamine released from the mucosal mast cell which may interact with capsaicin-sensitive sensory nerves, and 3) L-NAME unmasks the acid stimulatory response by suppressing the inhibitory mechanism.
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PMID:Mechanism of acid secretory changes in rat stomach after damage by taurocholate: role of nitric oxide, histamine, and sensory neurons. 907 52

The stomach normally responds to mucosa-damaging agents by decreasing acid secretion, but this acid response turn from "inhibition" into "stimulation" when the production of nitric oxide (NO) is inhibited by NG-nitro-L-arginine methyl ester (L-NAME). We investigated the mechanism underlying stimulation of acid secretion in the stomach after damage with taurocholate (TC) in the presence of L-NAME. A rat stomach was mounted in an ex vivo chamber and perfused with saline, and the potential difference (PD), luminal pH, and acid secretion were measured before and after application of 20 mM TC for 30 min. Exposure of the stomach to TC caused a reduction in PD, an increase in luminal pH, and a decrease in acid secretion. Pretreatment with L-NAME did not affect basal acid secretion but significantly increased secretion after damage with TC, without any effect on PD. This effect of L-NAME was antagonized by co-administration of L-arginine but not D-arginine. The luminal appearance of NO was also increased after exposure of the stomach to TC, a phenomenon completely blocked by L-NAME, or when EGTA was applied together with TC. The enhanced acid secretory response in the presence of L-NAME was inhibited by prior administration of cimetidine, FPL-52694 (a mast cell stabilizer), spantide (a substance P antagonist), or by chemical ablation of capsaicin-sensitive sensory neurons. Mucosal exposure to TC increased histamine output in the lumen and decreased the number of mucosal mast cells in the stomach. These changes were prevented by FPL-52694 or sensory neuronal ablation. These results suggest that (a) damage in the stomach may activate acid stimulation in addition to an NO-dependent inhibitory mechanism but that the latter effect overcomes the former, resulting in a decrease in acid secretion, (b) acid stimulation in the damaged stomach may be mediated by histamine released from the mucosal mast cells, a process that may interact with capsaicin-sensitive sensory nerves, and (c) L-NAME unmasks the acid stimulatory response by suppressing the inhibitory mechanism.
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PMID:Nitric oxide, histamine, and sensory nerves in the acid secretory response in rat stomach after damage. 947 25

Both tachykinins and leukotrienes (LTs) have been demonstrated to be the mediators for hyperpnea-induced bronchoconstriction (HIB) of guinea pigs. We tested the hypothesis that leukotrienes modulate HIB indirectly by triggering tachykinin release. Ninety nine young guinea pigs were divided into four groups: control; LTC4; FPL 55712 (a LT receptor antagonist); and MK-886 (an inhibitor of LT synthesis). Each animal was anesthetized, cannulated, paralyzed, and artificially ventilated. The protocol included the baseline, hyperpnea, and recovery periods. Thus, animals in each group were further divided into three subgroups: baseline; recovery-3 min; and recovery-8 min. We measured dynamic respiratory compliance (Crs), forced expiratory volume in 0.1 s (FEV0.1) and maximal expiratory flow at 30% total lung capacity (Vmax30), as well as determined substance P (SP) and LT levels in plasma and bronchoalveolar lavage (BAL) during either the baseline or the recovery (3 or 8 min) period. Hyperpnea caused decreases in Crs, FEV0.1 and Vmax30, indicating HIB, in the control group at 3 min and 8 min of the recovery period. Both FPL 55712 and MK-886 significantly attenuated HIB. In the control group, hyperpnea caused significant increases in SP and LT levels in both plasma and BAL. These increases in SP levels were significantly suppressed, however, by FPL 55712 and MK-886. Compared to the control group, infusion of LTC4 did not significantly alter either HIB, SP or LT levels in most cases. An additional group of 24 animals treated with neurokinin-2 receptor antagonist, SR 48968, demonstrated that SR 48968 significantly suppressed hyperpnea-induced increases in plasma, but not in BAL, LT levels. Since FPL 55712 and MK-886 first suppress LT activities, these results suggest that suppressed LT activities attenuate HIB indirectly via reducing tachykinin release.
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PMID:Mediators in hyperpnea-induced bronchoconstriction of guinea pigs. 1059

Leukotrienes (LTs), tachykinins (TKs), and oxygen radicals have been suggested to be important modulating factors for the hyperpnea-induced bronchoconstriction (HIB) of guinea pigs. In this study, we tested the hypothesis that LTs and oxygen radicals modulate HIB by triggering TK release. Eighty-five Hartley guinea pigs were divided into four groups: control, dimethylthiourea (DMTU), FPL 55712, and A63162. DMTU is the scavenger for hydroxyl radical. FPL 55712 is an antagonist of LT receptor, whereas A63162 is an inhibitor of lipoxygenase. Each group was further divided into three subgroups: baseline, hyperpnea, and recovery. Each animal was anesthetized, cannulated, paralyzed, and artificially ventilated. We measured dynamic respiratory compliance (Crs), maximal expiratory flow at 50% total lung capacity (V(max(50))), and forced expiratory volume in 0.1 s (FEV(0.1)) during the baseline and recovery periods. Hyperpnea caused significant decreases in Crs, V(max(50)), and FEV(0. 1), indicating HIB in the control group. Pretreatment with DMTU, FPL 5712, or A63162 attenuated HIB. Plasma substance P (SP) levels increased progressively during the experiment in all groups. However, both FPL 55712 and A63162, but not DMTU, significantly decreased SP levels. Similarly, lung malondialdehyde (MDA) contents increased progressively during the experiment in the control group. Neither FPL 55712 nor A63162 significantly affected the increase. On the contrary, DMTU significantly attenuated the increase in MDA during the recovery period. These results suggest that inhibition of LTs leads to suppression at SP levels and HIB, whereas DMTU attenuates HIB by means of other mechanisms.
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PMID:Mediators and oxygen radicals in hyperpnea-induced airway constriction of guinea pigs. 1096 May 56


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