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 effects of the bradykinin receptor selective antagonist, Hoe 140, and of the tachykinin NK-1 receptor antagonist (+/-)CP 96,345 were investigated in a rat model of chemically-induced cystitis (intravesical instillation of xylene in female rats). Intravenous injection of bradykinin (1 mumol./kg.) or substance P (3 nmol./kg.) produced plasma protein extravasation (PPE) in the rat urinary bladder. Bradykinin response was prevented by Hoe 140 (100 nmol./kg. intravenously) and unaffected by (+/-)CP 96,345 (10 mumol./kg. intravenously). Plasma protein extravasation produced by substance P was inhibited by (+/-)CP 96,345 but unchanged by Hoe 140. Catheterization required for intravesical xylene instillation into the female rat bladder produced per se an inflammatory response which was abolished by either Hoe 140 or (+/-)CP 96,345. Intravesical instillation of xylene produced a large PPE response which was reduced by about 65% by Hoe 140 or (+/-)CP 96,345. Combined administration of the two antagonists produced an additive effect on the PPE response to xylene. We conclude that both bradykinin and tachykinins are involved in the inflammatory reaction of the rat urinary bladder to catheterization and xylene irritation.
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PMID:Effect of bradykinin and tachykinin receptor antagonist on xylene-induced cystitis in rats. 768 30

Bradykinin- and substance P (SP)-stimulated second messenger studies in isolated subsets of neuroglia showed bradykinin-stimulated synthesis of phosphoinositides (PI) in type-1 astrocytes and oligodendrocytes. SP-stimulated PI accumulation was restricted to oligodendrocyte/type-2 astrocyte progenitor cells and type-2 astrocytes. These data were confirmed by analysis of calcium transients in single cells. In a regional study, SP-stimulated PI accumulation in primary astrocyte cultures was restricted to white matter. We conclude that regional heterogeneity in the expression of peptide receptors in cultures of primary astrocytes arises from a restricted distribution on subsets of macroglia. SP receptors restricted on cells of the oligodendrocyte/type-2 astrocyte type-2 lineage in vitro, coupled with in vivo observations by others, suggests that SP receptor expression is conserved on subsets of macroglia in vitro and possibly reactive astrocytes in vivo.
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PMID:Substance P receptors on O-2A progenitor cells and type-2 astrocytes in vitro. 768 42

In anesthetized rats increasing ureteral pressure results in an increase in ipsilateral afferent renal nerve activity and a reflex increase in contralateral urine flow rate and urinary sodium excretion that is dependent on intact prostaglandin synthesis. Activation of renal pelvic substance P receptors contributes to the renorenal reflex responses to increased ureteral pressure. Because these data suggested that renal sensory receptors could be activated by both prostaglandins and substance P we examined whether activation of renal sensory receptors by substance P was dependent on intact prostaglandin synthesis. The renal pelvis was perfused with capsaicin, 2.5 micrograms/ml, or substance P, 4 micrograms/ml, before and during renal pelvic perfusion with the prostaglandin synthesis inhibitor indomethacin, 50 micrograms/ml. Indomethacin reduced the peak ipsilateral afferent renal nerve activity responses to capsaicin and substance P by 83 +/- 15% and 81 +/- 8%, respectively, as well as the contralateral diuretic and natriuretic responses. We also examined the effects of renal pelvic administration of indomethacin on the responses to renal pelvic perfusion with bradykinin. Bradykinin, 20 micrograms/ml, increased peak ipsilateral afferent renal nerve activity by 197 +/- 47% and contralateral urine flow rate and urinary sodium excretion by 31 +/- 6 and 20 +/- 6%, respectively. Indomethacin reduced the ipsilateral afferent renal nerve activity response by 76 +/- 9% and abolished the contralateral diuretic and natriuretic responses to bradykinin. We conclude that renal sensory receptor activation by capsaicin, substance P, and bradykinin is dependent on intact renal prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of prostaglandins in renal sensory receptor activation by substance P and bradykinin. 769 51

An isolated perfused lung model was developed in which the mechanisms of regulation of sensory neuropeptide overflow and bronchoconstrictor responses evoked by antidromic vagal nerve stimulation or various irritants could be studied. For further comparison, non-adrenergic non-cholinergic (NANC) bronchoconstriction was also studied in guinea-pig isolated bronchus and in vivo. In the isolated guinea-pig lung, spontaneous strong postmortem bronchoconstriction occurred; this had to be overcome by the beta 2-adrenoceptor agonist terbutaline. Vagal stimulation, capsaicin, resiniferatoxin (RTX), nicotine, and pH 5 buffer all caused sensory peptide release and bronchoconstriction via a capsaicin-sensitive mechanism. Bradykinin and histamine also stimulated sensory peptide release but evoked bronchoconstriction mainly via capsaicin-resistant mechanisms. Stimulation at low frequency (1 Hz) caused similar degree of sensory nerve activation (peptide release in perfused lung and NANC bronchial contraction in bronchus) as stimulation at 10 Hz. Dactinomycin and the non-peptide SR 48968 selectively blocked the bronchoconstriction induced by neurokinin 2 (NK2) receptor agonists and also depressed that induced either by vagal stimulation or capsaicin, with no prejunctional effect on the overflow of calcitonin gene-related peptide (CGRP). Furthermore, SR 48968 inhibited the bronchoconstriction to citric acid aerosol. The NK1 antagonist CP 96345 had only marginal effects on NANC bronchoconstriction. Tetrodotoxin (TTX) and omega-conotoxin (CTX) inhibited neuropeptide release and bronchoconstriction caused by vagal stimulation or a low concentration of capsaicin but only marginally attenuated the effects evoked by a high concentration of capsaicin, or nicotine. Prejunctional alpha 2-adrenoceptor or opiate receptor activation inhibited the neuropeptide release and bronchoconstriction induced by vagal stimulation or a low concentration of capsaicin. Ruthenium red had a selective inhibitory effect on the overflow of neuropeptides [CGRP, neurokinin A (NKA)] and bronchoconstriction induced by capsaicin and its analogue RTX but not on responses induced by vagal stimulation, nicotine, bradykinin and histamine. It also inhibited CGRP and NKA release and bronchoconstriction caused by pH 5 buffer in lung, as well as cough and nasal irritation provoked by citric acid in vivo. The capsaicin receptor antagonist capsazepine inhibited peptide (CGRP, NKA) release and bronchoconstriction produced by capsaicin but not that evoked by vagal stimulation, nicotine and bradykinin, suggesting selectivity. Citric acid (in vivo) and pH 5 buffer (in vitro) produced bronchoconstriction via activation of capsaicin-sensitive sensory nerves. Interestingly, capsazepine also markedly depressed peptide overflow and bronchoconstriction caused by pH 5 buffer in isolated guinea-pig lung.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of neuropeptide release from pulmonary capsaicin-sensitive afferents in relation to bronchoconstriction. 769 42

Bradykinin, substance P and vasopressin induced a vasodilatation followed by a vasoconstriction in control perfused canine basilar arteries with endothelium. The dilatation was significantly reduced and the constriction was significantly enhanced by endothelial removal with saponin. The potentiated constriction was significantly blocked by sodium ozagrel, a thromboxane synthetase inhibitor. These results suggest that the dilatation due to these neuropeptides may depend on endothelium-derived relaxing factor, and that the augmented constriction after endothelial removal may be related to the thromboxane A2 production in cerebral arterial smooth muscles. This mechanism following the damage of endothelium might be implicated in cerebral vasospasm after subarachnoid haemorrhage.
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PMID:Origin of thromboxane-mediated constriction due to neuropeptides in canine basilar artery. 782 46

The stainless steel cannula method was applied to isolated and perfused canine basilar arteries to examine the role of endothelium in the responses to intraluminal vasoactive substances. After intraluminal treatment with saponin to remove the endothelium, the monophasic constrictions to potassium chloride and prostaglandin F2 alpha were potentiated, while those to phenylephrine (alpha 1-adrenoceptor agonist) and 5-hydroxytryptamine were not changed. Xylazine (alpha 2-adrenoceptor agonist) and acetylcholine induced a constriction preceded by a small dilation in controls. The response to xylazine was not modified, while the constriction to acetylcholine was augmented after endothelium removal. Bradykinin, substance P and vasopressin caused a dilation in lower doses, and a dilation followed by a secondary constriction in higher doses in controls. The dilations to these peptides were reduced and the constrictions were enhanced after endothelial removal. Adenosine triphosphate produced a biphasic response, i.e., a dilation followed by a constriction, which was occasionally preceded by a small constriction in higher doses, and only the dilation in lower doses was attenuated. The monophasic dilation to adenosine was potentiated, while the papaverine-induced dilation was not influenced by endothelial removal. After extraluminal treatment with oxyhemoglobin, the dilations to calcium ionophore A23187 and thimerosal were attenuated, while the constriction to acetylcholine was enhanced. The dilations to substance P and vasopressin were depressed, and the constrictions were potentiated. The monophasic dilation to sodium nitroprusside was augmented, while that to papaverine was not changed. These results suggest that the endothelium may play important roles not only in producing endothelium-derived relaxing factors but also in modulating the calcium influx into the smooth muscle cells. The mechanisms of altered responsiveness might be implicated in cerebral vasospasm following subarachnoid hemorrhage.
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PMID:Effects of endothelium removal by saponin and of oxyhemoglobin on canine cerebrovascular responses. 783 71

1. Human epicardial coronary artery rings, freshly obtained from cardiac transplant patients, were examined for their responses to endothelium-derived relaxing factor (EDRF)-releasing agents. 2. Functional antagonism profoundly influenced relaxation responses in this tissue. Increasing force with concentrations of U46619 above 3 nM (40% of maximum contraction response) resulted in a reduction of the maximum response to four vasorelaxants which relax vascular smooth muscle via different mechanisms: the EDRF-releasing agents, substance P and bradykinin; the endothelium-independent nitro-vasodilator, sodium nitroprusside (SNP); and the beta-adrenoceptor agonist, isoprenaline. 3. Substance P, histamine, bradykinin and the Ca2+ ionophores ionomycin and A23187 all caused concentration- and endothelium-dependent relaxation in vessels pre-contracted with the thromboxane A2-mimetic, U46619 (3 nM) to an active force optimal for relaxation responses. Nifedipine (0.1 microM), added to prevent spontaneous contractions, had no effect or relaxation responses to substance P, bradykinin and histamine. 4. Substance P was the most potent of the EDRF-releasing agents examined and all agents except for bradykinin caused near-maximal relaxation. Bradykinin caused only 46.2% +/- 7.3% relaxation. Responses were abolished when the endothelium was removed and, except for histamine, were not significantly affected by indomethacin (3-10 microM, P > 0.05). Histamine (0.1-10 microM) caused a concentration-dependent contraction of arterial rings without endothelium. 5. The L-arginine analogues NG-nitro-L-arginine (L-NOARG, 0.1 mM) and NG-monomethyl-L-arginine (L-NMMA, 0.1 mM) both caused no further contraction in arteries precontracted with U46619 (3 nM) and were in general, poor inhibitors of responses to EDRF agonists. L-NMMA, but not L-NOARG,caused small but significant decreases in the maximum responses to substance P, bradykinin (18.5 +/- 6.9% and 27.6 +/- 10.9% relaxation with L-NMMA and L-NOARG, respectively), histamine and A23187 (P<0.05). The analogues had no effect on SNP responses.6. In conclusion, EDRF release in human isolated coronary artery is only poorly antagonized by the nitric oxide synthase inhibitors L-NOARG and L-NMMA. These results indicate that either the nitricoxide transduction pathway present in human coronary artery is different from that in other tissues or that another factor(s) (e.g. endothelium-derived hyperpolarizing factor) is also released in response to EDRF-releasing agents and augments the relaxation to nitric oxide.
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PMID:Pharmacological reactivity of human epicardial coronary arteries: characterization of relaxation responses to endothelium-derived relaxing factor. 788 60

In the present study, we demonstrated the inhibitory effect of magnolol on the plasma leakage in passive cutaneous anaphylactic (PCA) reaction, neurogenic inflammation, dorsal skin and ear edema in mice. Hind-paw skin plasma extravasation caused by antidromic stimulation of the saphenous nerve was reduced in mice pretreated with magnolol, diphenydramine or methysergide, but not with indomethacin. Ear edema formation in the PCA reaction was reduced by magnolol in dose-dependent manner. In addition, histamine-, serotonin-, compound 48/80-, bradykinin- and substance P-induced ear edema in mice was also suppressed by magnolol. A dose- and time-dependency of the inhibitory effect of magnolol was demonstrated in histamine- and compound 48/80-induced dorsal skin edema. The maximal inhibitory effect produced by a single dose of magnolol (10 mg/kg) persisted for 1 h, and significant suppression lasted for at least 3 h. In compound 48/80-pretreated mice, the histamine content of the ear was greatly reduced. Bradykinin- and substance P-induced ear edema in compound 48/80-pretreated mice was less severe than that seen in normal mice, but was still significantly reduced by magnolol pretreatment. Moreover, the inhibitory effect of magnolol was more marked than that of diphenhydramine combined with methysergide. These results suggest that the inhibitory effect of magnolol on local edema formation probably occurs through a nonselective inhibition on vascular tissue to prevent the permeability change caused by various mediators.
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PMID:The inhibitory effect of magnolol on cutaneous permeability in mice is probably mediated by a nonselective vascular hyporeactivity to mediators. 813 9

Like indomethacin, BW755C, diphenhydramine and methysergide, 2-phenyl-4-quinolone (YT-1) suppressed the polymyxin B-induced hind-paw edema. This inhibitory effect of YT-1 was also demonstrated in adrenalectomized mice. YT-1 inhibited the antidromic stimulation of saphenous nerve-induced plasma leakage in dorsal paw skin and reduced the volume of plasma exudation in PCA reaction. Bradykinin-, substance P- and compound 48/80-induced mouse ear edema was suppressed by YT-1 in a dose-dependent manner. In isolated rat peritoneal mast cells, YT-1 produced a dose-dependent inhibition of bradykinin-, substance P- and compound 48/80-induced histamine and beta-glucuronidase release. YT-1 also reduced the TXB2 formation from PMN leukocytes with IC50 2.0 +/- 0.5 microM, however with little effect on LTB4 formation. Histamine- and serotonin-induced plasma exudation in ear edema were reduced by YT-1. Moreover, the maximal response of ileum contraction caused by histamine and serotonin were also suppressed by YT-1 in a dose-dependent manner. In compound 48/80-pretreatment mice, YT-1 failed to suppress the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine combined with methysergide did. These results indicate that the inhibitory effect of YT-1 on local edema formation is not through the release of steroid hormones from adrenal gland, and is probably by suppressing the release of chemical mediators from mast cells, inhibition of prostaglandins formation, and noncompetitive but selective protection of the vasculature against the histamine- and serotonin-induced plasma extravasation.
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PMID:Suppressive effect of 2-phenyl-4-quinolone (YT-1) on hind-paw edema and cutaneous vascular plasma extravasation in mice. 820 10

Bradykinin (BK) and related kinins excite primary sensory neurons, thus leading to the activation of sensory impulses. More recently, both functional and neurochemical evidence have been accumulated that BK evokes release of neuropeptides, including calcitonin gene-related peptide and the tachykinins substance P and neurokinin A, from peripheral terminals of capsaicin-sensitive primary afferents. The present article will review the mechanisms and the pathophysiological implications of the ability of BK to release sensory neuropeptides at the peripheral level. An account of the clinical studies performed on this subject will be also given.
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PMID:Sensory neuropeptide release by bradykinin: mechanisms and pathophysiological implications. 821 May 18


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