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)

ODU Plaque-susceptible rats (ODUS/Odu) exhibit markedly heavy plaque formation in the lower incisors and develop both periodontal pockets and gingivitis after being fed a commercially available powder diet. These rats have been established as an inbred strain. We have demonstrated that the ODUS/Odu are a very suitable experimental model for studying periodontitis. We already reported about the allelic distribution, changes of plaque formation and body weight, biochemical nature, toxic activity, vascular permeability factor and bradykinin inactivating factor of the plaque, histological and immunological studies, the pH in the periodontal pocket, amount of saliva, IgA in the saliva, salivary kallikrein, the relationship between sialic acid in the saliva and the serum, leukocyte functions (chemotaxis and superoxide anion) in ODUS/Odu, histamine, mast cell, free radicals, superoxide dismutase activities in gingiva and gingival nerve fibers with substance P or calcitonin gene-related peptide, and effect of diabetes. Streptozotocin-induced diabetic ODUS/Odu may be a useful tool for studying the pathological mechanisms in the development of periodontal tissue breakdown in diabetes. ODUS/Odu should help to further establish the utility of this strain as a model for experimental periodontal disease.
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PMID:[Experimental periodontitis in rats]. 762 82

Electrical-field stimulation caused an endothelium-dependent relaxation in rabbit aorta rings precontracted by phenylephrine. The relaxation was reduced in a dose-dependent manner by morphine, benzalkonium, [D-Pro2,D-Trp7,9]substance P and an beta-adrenoceptor antagonist, propranolol. The vasodilatation was enhanced by superoxide dismutase and abolished by haemoglobin and NG-monomethyl-L-arginine. The inhibitory effect of NG-monomethyl-L-arginine was reversed by L-arginine, the precursor of nitric oxide biosynthesis, but not by its enantiomer, D-arginine. These data show that the electrically induced relaxation is independent on nitric oxide released by NK receptors and beta-receptors. Moreover, morphine, by reducing substance P release, decreased the magnitude of electrically induced relaxation, suggesting an indirect role of opioids in the regulation of the peripheral circulation through the control of nitric oxide release. Furthermore our observations confirm the hypothesis that subtypes of beta-adrenoceptors releasing nitric oxide participate in the regulation of vascular tone.
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PMID:Involvement of NK receptors and beta-adrenoceptors in nitric oxide-dependent relaxation of rabbit aorta rings following electrical-field stimulation. 769 17

This study investigated the relationship between oxygen radicals and exsanguination-induced bronchoconstriction using antioxidant in guinea pigs. To accomplish this, two phases of studies were carried out. In phase 1, 34 guinea pigs weighing 342 +/- 11 g were divided into five groups: control (n = 7); acute dimethylthiourea (DMTU, n = 7); chronic DMTU (n = 8); superoxide dismutase (SOD, n = 6); and catalase (n = 6). Animals in the control group were not treated. DMTU, SOD, and catalase were employed for the scavenging of hydroxyl radical, superoxide anion, and hydrogen peroxide, respectively. Ten additional guinea pigs weighing 293 +/- 6 g were divided into two groups in phase 2: sham (n = 6) and chronic apocynin (n = 4). Animals in the sham group received injections of the vehicle, whereas apocynin was used to suppress the production of superoxide anion. All animals were anesthetized, sternotomized, and artificially ventilated. Before (baseline) as well as at fixed intervals 5-30 minutes following the exsanguination, the maximal expiratory flow maneuver was performed and the dynamic compliance (Cdyn) was obtained. Decreases in the maximal expiratory flow at 50% baseline vital capacity and Cdyn were used as indicators of bronchoconstriction. Exsanguination in the control and sham groups caused a gradual increase in airway constriction with time that was significantly ameliorated by chronic DMTU and chronic apocynin pretreatments but was not affected by other acute treatments. These results indicate that chronic treatment with antioxidants ameliorates exsanguination-induced, tachykinin-mediated airway constriction.
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PMID:Oxygen radicals in exsanguination-induced bronchoconstriction of guinea pigs. 793 52

Coronary artery contractility is well known to be modulated by oxygen partial pressure. Both smooth muscle and the endothelium contribute to coronary artery oxygen sensitivity. Mechanisms underlying endothelium-dependent effects of oxygen include the sensitivity of the nitric oxide/endothelium-derived relaxing factor (EDRF), hydrogen peroxide, and eicosanoid pathways. In the present study, we characterize a novel endothelium-dependent component of porcine coronary artery oxygen sensitivity that is independent of these known pathways. Porcine coronary arteries were stimulated with either KCl or U46619. Hypoxia elicited a transient increase in force that was much greater in endothelium-intact arteries. This effect was abolished by nitric oxide/EDRF pathway inhibitors NG-monomethyl-L-arginine and N-nitro-L-arginine. In the steady state, hypoxia reduced isometric force to a similar degree in both intact and denuded arteries. Reoxygenation elicited a rapid and transient relaxation only in intact arteries. In contrast, this endothelium-dependent relaxation was not inhibited by nitric oxide/EDRF pathway inhibitors nor inhibitors of other potential oxygen-sensitive pathways, such as indomethacin, aminotriazole, superoxide dismutase, catalase, propranolol, or ouabain. The reoxygenation relaxation was, however, sensitive to very low levels of oxygen and was inhibited by cyanide and rotenone, suggesting an involvement of mitochondrial metabolism. Interestingly, the relaxation response to reoxygenation, similar to that for substance P, could be restored in denuded arteries by coupling with an endothelium-intact donor artery. This "sandwich" experiment suggests that the endothelium dependence is mediated by a transmissible factor. Our results indicate that a novel class of endothelium-dependent factors may contribute to coronary artery responses to changes in oxygen partial pressure.
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PMID:Reoxygenation-induced relaxation of coronary arteries. A novel endothelium-dependent mechanism. 815 34

In the airways and lungs, activated afferent C-fibers release tachykinins, which induce noncholinergic bronchoconstriction. We have, for several years, focused our research on the role of axon reflex and oxygen radicals in noncholinergic airway constriction in guinea pigs. In this species, the noncholinergic bronchial constriction is not affected by administration of a ganglionic blocking agent, chlorisondamine, indicating that only the afferent C-fiber, not a complete reflex arc, is required for this constriction. Accordingly, we investigated the role of axon reflex by using tetrodotoxin (TTX) and bupivacaine to block impulse conduction in the axon. For the role of oxygen radicals, superoxide dismutase (SOD), catalase (CAT), and dimethylthiourea (DMTU) were employed to scavenge superoxide anion, hydrogen peroxide, and hydroxyl radical, respectively. We used capsaicin, resiniferatoxin (RTX), or hyperventilation to activate afferent C-fibers which, in turn, release tachykinins and lead to noncholinergic airway constriction. The constriction was quantified by measuring the maximal expiratory flow rate (Vmax) and dynamic compliance (Crs). Both capsaicin and RTX caused an immediate decrease in Vmax and Crs, indicating severe bronchoconstriction. This constriction decreased gradually with time. Tachykinin depletion abolished neurotoxin-induced airway constriction, suggesting that tachykinins mediate the constriction. Both TTX and bupivacaine significantly attenuated the constriction at 15-20 min after neurotoxin administration. Therefore, these data suggest that the axon reflex plays an important role in noncholinergic bronchial constriction. In other studies, capsaicin- or hyperventilation-induced bronchoconstriction was abolished by tachykinin depletion, as well as significantly ameliorated by the administration of antioxidants. These data indicate that oxygen radicals modulate the tachykinin-mediated noncholinergic airway constriction.
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PMID:Noncholinergic airway constriction: role of axon reflex and oxygen radicals. 819 89

Endogenous nitric oxide (NO, endothelium-derived relaxing factor) was stimulatory for histamine- and suppressive for serotonin-induced paw edema of mice. This action was mediated by guanosine 3',5'-cyclic monophosphate production. Local injection of superoxide dismutase (SOD), catalase, NG-monomethyl-L-arginine (L-NMMA), methylene blue and Desferal (iron chelator) mixed with mediator suppressed histamine-induced edema at doses between 0.1 and 100 micrograms/kg and showed no or little stimulatory effect at higher doses. L-arginine reversed the effect of L-NMMA. Serotonin edema was enhanced by a high dose of these drugs. Their effect became suppressive as the histamine ratio was increased in edema induced by a histamine-serotonin mixture. This suggested that serotonin-induced vascular permeability decreased with a greater production of either O2- or NO. Cimetidine (H2-antagonist) was not effective in histamine edema of normal mice, but became suppressive (ED50 = 70 micrograms/kg) when 10 mg/kg L-NMMA was coinjected. SOD and methylene blue also rendered this edema sensitive to cimetidine. A simultaneous decrease in sensitivity to mepyramine (H1-antagonist) indicated that NO and oxyradicals kept H1-receptors activated. L-NMMA had no effect on bradykinin edema, but suppressed thrombin-, acetylcholine-, platelet-activating factor-, substance P- and FeCl3-induced paw edemata. Nitroprusside (NO donator) suppressed serotonin edema. N-Acetylcysteine and cytochrome c, but not ascorbate and hydroxyl radical scavengers suppressed histamine edema.
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PMID:Opposite effect of superoxide dismutase, L-arginine analogues, methylene blue and desferal: suppression of histamine-induced and stimulation of serotonin-induced paw edema in mice. 835 90

The role of oxygen radicals in isocapnic hyperpnea-induced bronchoconstriction (HIB) of guinea pigs was investigated using scavengers of the radicals. In series 1, 50 young guinea pigs were randomly divided into seven groups: control 1, control 2, chlorisondamine, tetrodotoxin (TTX), acute dimethylthiourea (DMTU), tachykinin depletion, and 5% CO2 in air. Animals of the control 2 group received vehicle (saline) infusion while those of the control 1 group did not. Chlorisondamine was used to block ganglionic transmission, TTX to interrupt nerve conduction, DMTU to scavenge hydroxyl radicals, and chronic capsaicin pretreatment to deplete tachykinins. The animals in the last group were ventilated with dry 5% CO2 in air during hyperpnea. In series 2, 13 additional animals were used to test the effects of intratracheal administration of superoxide dismutase and catalase (SOD + CAT) on HIB. Each animal was anesthetized with pentobarbital sodium, cannulated with a tracheal cannula and venous catheter, paralyzed with gallamine triethiodide, and mechanically ventilated. During the baseline period, each animal was ventilated normally with humidified air. Then it was hyperventilated 15 min with a dry gas mixture of 95% O2-5% CO2, except animals in the last group of series 1. Subsequently, all animals returned to normal ventilation with humidified air for 45 min (recovery period). The maximal expiratory flow and dynamic compliance were obtained periodically during the recovery period. The isocapnic hyperpnea using 95% O2-5% CO2, but not 5% CO2 in air, caused bronchoconstriction that was significantly blocked by acute DMTU, acute SOD + CAT, and tachykinin depletion. In an additional group of six animals, acute DMTU did not significantly alter acetylcholine-induced airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen radicals in bronchoconstriction of guinea pigs elicited by isocapnic hyperpnea. 845 78

1. Cigarette smoke induces plasma exudation in the airways of rodents by activation of capsaicin-sensitive 'sensory-efferent' nerves. The response is mediated predominantly by substance P (SP) and the magnitude of exudation is regulated by neutral endopeptidase (NEP). The component(s) of the smoke responsible for the activation of the nerves may be reactive oxygen radicals. We investigated the effect of the hydroxyl radical scavenger dimethylthiourea (DMTU), a regulator of superoxide anion, superoxide dismutase (SOD), and a regulator of hydrogen peroxide, catalase, on plasma exudation (measured using Evans blue dye) induced by cigarette smoke in guinea-pig main bronchi in vivo. The effect of DMTU on plasma exudation and non-cholinergic bronchoconstriction (measured as pulmonary insufflation pressure, PIP) induced by electrical stimulation of the vagus nerves was also assessed. Interaction between hydroxyl radicals and NEP was assessed with the NEP inhibitor phosphoramidon. 2. In each of the experiments, cigarette smoke increased plasma exudation by approximately 200% above air-exposed controls. Acute administration of DMTU (1.5 g kg-1, i.v. for 20 min) significantly reduced cigarette smoke-induced plasma exudation by 69%. In contrast, neither SOD (240,000 u kg-1, i.v.) nor catalase (400,000 u kg-1, i.v.) significantly affected the exudative response. 3. Chronic pretreatment with DMTU (1.25 g kg-1 over 4 days) significantly reduced bronchial plasma exudation induced by cigarette smoke by 72%. Phosphoramidon (1.5 mg kg-1, i.v.) completely reversed the inhibition by DMTU of cigarette smoke-induced plasma exudation. 4. Vagal stimulation increased plasma exudation by approximately 200% and PIP by approximately 250%. Acute treatment with DMTU had no significant inhibitory effect on these responses, whereas chronic pretreatment inhibited them by approximately 80%. Phosphoramidon reversed the inhibition by chronic DMTU. 5. SP (1 nmol kg-1) increased plasma exudation by approximately 250%, a response which was not inhibited by either acute or chronic DMTU. 6. We conclude that hydroxyl radicals, rather than superoxide anion or hydrogen peroxide, are involved in the induction of neurogenic plasma exudation and bronchoconstriction induced by cigarette smoke or by electrical stimulation of the vagus nerves. These radicals also affect the activity of NEP. Acute DMTU may affect directly the neural actions of hydroxyl radicals contained in the cigarette smoke. Chronic pretreatment with DMTU may inhibit the neurogenic airway responses by effects on tachykinin biosynthesis and/or axonal transport.
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PMID:Involvement of hydroxyl radicals in neurogenic airway plasma exudation and bronchoconstriction in guinea-pigs in vivo. 882 33

To test the hypothesis that oxygen radicals play an important role in the nonvagal component of the noncholinergic bronchoconstriction in vivo, 37 guinea pigs weighing 329 +/- 8 g were randomly divided into five groups: group 1, vagotomy; group 2, vagotomy + CAT (catalase); group 3, vagotomy + SOD (superoxide dismutase); group 4, vagotomy + PBN (alpha-phenyl-N-tert-butyl nitrone); and group 5, capsaicin pretreatment. CAT, SOD, and PBN are antioxidants. Each animal was anesthetized, paralyzed, artificially ventilated, and pretreated with atropine and phenoxybenzamine. Immediately after acute capsaicin challenge, animals in group 1 exhibited decreases in maximal expiratory flow, dynamic respiratory compliance, and total lung capacity, as well as an increase in functional residual capacity, indicating noncholinergic airway constriction. The bronchoconstriction was significantly ameliorated by SOD and PBN, and it was almost abolished by capsaicin pretreatment. Thirty minutes after acute capsaicin challenge, there was a significant decrease in airway NEP activity and an increase in lung substance P level in group 1 but not in other groups. These results indicate that nonvagal component of noncholinergic bronchoconstriction is partially modulated by oxygen radicals.
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PMID:Oxygen radicals in the nonvagal component of noncholinergic airway constriction. 889 67

1. The generation of superoxide anions (O2-) by intact pig coronary artery rings was measured using a lucigenin-enhanced chemiluminescence technique and a histochemical technique with Nitroblue Tetrazolium (NBT) staining. 2. Isolated arteries with intact endothelium generated O2- at a rate of 9.0 +/- 0.8 pmol min-1 (mg dry weight)-1; this rate was diminished by about 24% when the endothelium was removed. The NBT staining of arterial ring preparations showed formazan precipitation mainly in the intima. Arterial rings were pretreated with diethylthiocarbamate in order to inhibit Cu-Zn superoxide dismutase (SOD) activity which increased the O2- generation by 184 +/- 55% (n = 10; P < 0.01). Stimulation of protein kinase C with phorbol 12-myristate 13-acetate (5 microM) enhanced endothelium-dependent O2- generation by 136 +/- 20% (n = 19; P < 0.01). Neither stimulation with bradykinin or substance P, nor inhibition with NG-nitro-L-arginine methyl ester of endothelial nitric oxide synthase had a significant effect on O2- generation. In contrast, the inhibition of flavoproteins with diphenyliodonium decreased concentration-dependent O2- generation (IC50, 1.85 +/- 5.33 microM). Inhibition of tetrahydrobiopterin synthesis with 2,4-diamino-6-hydroxy-pyrimidine resulted in a reduced generation of O2- by about 55%. 3. The addition of 100 microM NADH and 100 microM NADPH resulted in an excessive generation of O2- at a rate of 0.68 +/- 0.03 and 0.26 +/- 0.01 nmol O2- min-1 (mg protein)-1, respectively, in the membrane fraction, but not in the cytosolic fraction, of homogenates obtained from arteries. 4. The results suggest that intact coronary arteries do generate O2- under basal conditions and that the endothelial layer significantly contributes to this phenomenon. This generation of O2- is greatly influenced by intrinsic SOD activity. It is suggested that basal vascular O2- generation is mainly due to membrane-bound NAD(P)H oxidase activity and/or tetrahydrobiopterin-dependent processes.
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PMID:Endothelial-derived superoxide anions in pig coronary arteries: evidence from lucigenin chemiluminescence and histochemical techniques. 914 21


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