Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of bradykinin on nociceptors have been characterized on a preparation of the neonatal rat spinal cord with functionally connected tail maintained in vitro. Administration of bradykinin to the tail activated capsaicin-sensitive peripheral fibres and evoked a concentration-dependent (EC50 = 130 nM) depolarization recorded from a spinal ventral root (L3-L5). 2. The response to bradykinin was unaffected by the peptidase inhibitors, bestatin (0.4 mM), thiorphan (1 microM), phosphoramidon (1 microM) and MERGETPA (10 microM) or by the presence of calcium blocking agents, cadmium (200 microM) and nifedipine (10 microM). 3. Inhibition of cyclo-oxygenase with indomethacin (1-5 microM), aspirin (1-10 microM) and paracetamol (10-50 microM) consistently attenuated responses to bradykinin. 4. The effect of bradykinin was mimicked by the phorbol ester PDBu, an activator of protein kinase C. The response to bradykinin was attenuated following desensitization to PDBu but desensitization to bradykinin did not induce a cross-desensitization to PDBu. The protein kinase C inhibitor staurosporine (10-500 nM) consistently attenuated the effects of PDBu and bradykinin. 5. Bradykinin responses were reversibly enhanced by dibutyryl cyclic AMP (100 microM). However dibutyryl cyclic GMP (0.5 mM) and nitroprusside (10 microM) produced prolonged block of responsiveness to bradykinin. Prolonged superfusion with pertussis toxin did not affect responses to bradykinin. 6. The B1-receptor agonist des Arg9-bradykinin (10-100 microM) was ineffective alone or after prolonged exposure of the tail to lipopolysaccharide (100 ng ml-1) or epidermal growth factor (100 ng ml-1) to induce B1 receptors. The BI-receptor antagonist, des Arg9 Leu8-bradykinin (10 JM) did not attenuate the response to bradykinin. A number of bradykinin B2 antagonists selectively and reversibly attenuated the response to bradykinin. The rank order potency was Hoe 140> LysLys [Hyp3,Thi5 8,D-Phe7]-bradykinin> D-Arg[Hyp3, Thi5'8, D-Phe7]-bradykinin = D-Arg[Hyp2,Thi5'8, D-Phe7]-bradykinin.7. These data show that bradykinin produces concentration-dependent activation of peripheral nociceptors in the neonatal rat tail. The responses were unaffected by calcium channel block and were partially dependent on the production of prostanoids. Bradykinin-evoked responses were consistent with the activation of protein kinase C-dependent mechanisms. Cyclic GMP-dependent mechanisms may be involved in bradykinin-receptor desensitization whereas cyclic-AMP dependent mechanisms increase fibre excitability and facilitate bradykinin-induced responses. The effects of bradykinin were mediated by a B2 receptor.
 ...
PMID:Bradykinin-induced activation of nociceptors: receptor and mechanistic studies on the neonatal rat spinal cord-tail preparation in vitro. 133 51

Bradykinin enhances prostanoid synthesis in aorta smooth muscle cells. Free arachidonic acid also enhances prostanoid synthesis and bradykinin, unlike fatty acid releasing agents, has a synergistic effect with free arachidonic acid. Bradykinin promotes metabolite release from cells prelabeled with [14C]-arachidonic acid and this effect is blocked completely by indomethacin. High performance liquid chromatography shows increase amounts of labeled 6-keto-prostaglandin F1 alpha, prostaglandin E2 and three additional cyclooxygenase-dependent metabolites but no increase in free arachidonic acid or other metabolites either in the absence or presence of indomethacin. Fatty acid releasing agents such as A23187 and cyclosporine A have very different effects on cells. These agents enhance levels of prostanoids, a number of other cyclooxygenase-independent metabolites, and free arachidonic acid which is even more elevated with added indomethacin. Bradykinin behaves in all respects like another agent, bacterial lipopolysaccharide, and the action of both agents is consistent with a mechanism involving cyclooxygenase rather than fatty release in the arachidonic acid cascade.
 ...
PMID:Action of bradykinin at the cyclooxygenase step in prostanoid synthesis through the arachidonic acid cascade. 181 Jan 49

L-Arginine, the primary nitrogen source for nitric oxide synthesized by many cell types in culture and for biosynthesized nitrate in humans, is also a nitrogen source for biosynthesized nitrate in rats and ferrets. After administration of [15N2]L-arginine to rats and ferrets, [15N]NO3- was detected in urine. Escherichia coli lipopolysaccharide induced more than a 10-fold increase in urinary nitrate in rats and a parallel increase in incorporation of 15N from [15N2]L-arginine into NO3-. Bradykinin, a vasodilator which induces nitric oxide production by endothelial cells in vitro, lacked detectable effect on urinary nitrate or on incorporation of L-arginine nitrogen into nitrate in rats. A prolonged period of vasodilation brought on by an extended period of exercise increased urinary nitrate 2-fold in human subjects. In the rat, recoveries in 24 h post-dose urine collections of [15N]NO3- given i.v. and i.p. were 75 and 64% respectively, while in the ferret, recoveries of i.v. and per os [15N]NO3- doses were 49 and 34% respectively. Thus, nitrate synthesized by mammalian cells in vivo would undergo losses similar to those for exogenous nitrate.
 ...
PMID:Nitrate biosynthesis in rats, ferrets and humans. Precursor studies with L-arginine. 233 12

Bradykinin (BK) and its fragment des-Arg9-BK failed to stimulate thymidine incorporation in all but one observed fibroblast cultures derived from human amniotic fluid or rabbit dermis. The rabbit dermis fibroblast line designated R51 acquired the capacity to increase its DNA synthesis in response to kinins after several weeks in culture. It was more sensitive to des-Arg9-BK than to BK and the effect of both peptides was antagonized by the analog Leu8, des-Arg9-BK; these features are shared with certain smooth muscle preparations responsive to kinins such as the rabbit aorta. Recently isolated rabbit dermis or human amniotic fibroblasts could not be made responsive to kinins by pre-incubating them with bacterial lipopolysaccharide. The line R51 released more PGE2 than baseline when stimulated with BK or des-Arg9-BK at low concentrations; it was also doubling faster than recently isolated cells of similar origin.
 ...
PMID:Mitogenic effect of bradykinin and of des-Arg9-bradykinin on cultured fibroblasts. 346 53

1. The aim of the study was to assess the regional haemodynamic responsiveness to vasoconstrictor and vasodilator challenges during continuous 24 h infusion of lipopolysaccharide (LPS) in conscious Long Evans rats. 2. Rats were chronically instrumented for the measurement of regional haemodynamics (either internal and common carotid or renal, superior mesenteric and hindquarters) and received 3 min of infusions of acetylcholine (22 nmol min-1), methoxamine (120 nmol min-1), salbutamol (0.83 nmol min-1) and bradykinin (14.4 nmol min-1) at 2, 6 and 24 h after the start of saline or LPS (150 micrograms kg-1 h-1) infusion (rats with carotid probes received only acetylcholine and methoxamine). 3. During infusion of LPS there was a changing haemodynamic profile. After 2 h, there was a modest hypotension and vasodilatation in the internal carotid, renal and hindquarters vascular beds. After 6 h, arterial blood pressure had returned to baseline, there was still vasodilatation in the renal vascular bed but vasoconstriction in the internal and common carotids and the hindquarters. After 24 h, there was hypotension, tachycardia and generalized vasodilatation. 4. Acetylcholine caused a fall in blood pressure, tachycardia and hyperaemic vasodilatation in the carotid and renal vascular beds. Throughout the infusion of LPS, the carotid vasodilator response was enhanced after 2 h, reduced after 6 h and enhanced again after 24 h, whereas the renal vasodilator response to acetylcholine was either reduced (6 h) or absent (2 and 24 h); at this juncture the hypotensive response to acetylcholine was also enhanced and the tachycardia was reduced. 5. Methoxamine caused a rise in blood pressure, a fall in heart rate, and vasoconstriction in all the vascular beds monitored. During infusion of LPS, the pressor response to methoxamine was consistently reduced as were the vasoconstrictor responses in the carotid and mesenteric vascular beds, whereas the renal and hindquarters vasoconstrictor responses to methoxamine were only significantly reduced at some time points (renal 6 h, hindquarters 2 and 6 h).6. Salbutamol caused hypotension, tachycardia and hyperaemic vasodilatation, particularly in the hindquarters vascular bed. Throughout the infusion of LPS, the cardiovascular responses to salbutamol were substantially attenuated.7. Bradykinin caused hypotension, tachycardia and hyperaemic vasodilatation in the renal, mesenteric and hindquarters vascular beds. During the infusion of LPS, the hypotensive response to bradykinin was consistently augmented, and the tachycardia was consistently reduced, but the regional haemodynamic profile changed with time. Thus, after 2 h, the mesenteric vasodilator response was augmented and the hindquarters vasodilator response was reduced; after 6 h, the mesenteric vasodilator response appeared normal, but the renal and hindquarters vasodilator responses were reduced; after 24 h, the hindquarters vasodilator response was markedly augmented and the renal response had changed to a vasoconstriction.8. The present findings indicate marked regional variations in response to acetylcholine, methoxamine,salbutamol and bradykinin with time during LPS infusion. The changes observed are likely to reflect the interplay of a number of endogenous vasodilator and vasoconstrictor systems; further investigations will be required to clarify the mechanisms involved.
 ...
PMID:Regional haemodynamic responses to acetylcholine, methoxamine, salbutamol and bradykinin during lipopolysaccharide infusion in conscious rats. 795 64

1. The hyperalgesic activities in rats of bradykinin, carrageenin and lipopolysaccharide (LPS) were investigated in a model of mechanical hyperalgesia. 2. Bradykinin and carrageenin evoked dose-dependent hyperalgesia with maximum responses of similar magnitude to responses to LPS (1 and 5 micrograms). 3. Hoe 140, an antagonist of BK2 receptors, inhibited in a dose-dependent manner hyperalgesic responses to bradykinin, carrageenin and LPS (1 microgram) but not responses to LPS (5 micrograms), prostaglandin E2, dopamine, tumour necrosis factor alpha (TNF alpha), IL-1, IL-6 and IL-8. 4. Responses to bradykinin and LPS (1 and 5 micrograms) were inhibited by the cyclo-oxygenase inhibitor, indomethacin and by the beta-adrenoceptor antagonist, atenolol. The effects of indomethacin and atenolol were additive: their combination abolished responses to bradykinin and LPS (1 microgram) and markedly attenuated the response to LPS (5 micrograms). 5. Antiserum neutralizing endogenous TNF alpha abolished the response to bradykinin whereas antisera neutralizing endogenous IL-1 beta, IL-6 and IL-8 each partially inhibited the response. The combination of antisera neutralizing endogenous IL-1 beta+IL-8 or IL-6+IL-8 abolished the response to bradykinin. 6. Antisera neutralizing endogenous TNF alpha, IL-1 beta, IL-6 and IL-8 each partially inhibited responses to LPS (1 and 5 micrograms). Increasing the dose of antiserum to TNF alpha or giving a combination of antisera to IL-1 beta+IL-8 or IL-6+IL-8 further inhibited responses to LPS (1 and 5 micrograms). 7. These data show that bradykinin can initiate the cascade of cytokine release that mediates hyperalgesic responses to carrageenin and endotoxin (1 microgram). The lack of effect of Hoe 140 on hyperalgesic responses to LPS (5 microgram) suggests that the release of hyperalgesic cytokines can be initiated independently of bradykinin BK2 receptors.
 ...
PMID:Bradykinin initiates cytokine-mediated inflammatory hyperalgesia. 829 13

Using specific antisera for IL-1 beta and IL-8, as well as cyclooxygenase inhibitors and propranolol, we have demonstrated that these cytokines are responsible for the prostaglandin and sympathetic components of carrageenin-induced hyperalgesia in the rat paw test. The release of IL-1 beta and IL-8 is preceded by the liberation of TNF-alpha. We have also tested in a nociceptive model the effects of bradykinin and a specific bradykinin antagonist, HOE 140, on the hyperalgesia induced by carrageenin and lipopolysaccharide (LPS). Bradykinin-induced hyperalgesia was abolished by HOE 140 and by treatment of the paws with anti-TNF-alpha antisera. HOE 140 significantly inhibited the hyperalgesia induced by carrageenin and LPS. It is suggested that in these two models bradykinin is associated with the release of hyperalgesic cytokines.
 ...
PMID:Bradykinin release of TNF-alpha plays a key role in the development of inflammatory hyperalgesia. 831 26

Bradykinin (BK) and Tyr8-BK induced graded rat paw edema with EC50 values of 1.9 and 1.1 nmol/paw, while des-Arg9-BK (DABK, up to 300 nmol/paw) was marginally effective. Tyr8-BK, but not DABK, also caused a dose-related increase in mouse paw edema, with an EC50 of 1.3 nmol/paw. The response to Tyr8-BK (10 nmol/paw) in rat paw edema was antagonized by B2 receptor antagonists (HOE-140 or NPC 17731, 30 nmol/paw) but not by the B1 antagonist des-Arg9[Leu8]BK (DALBK, 100 nmol/paw). Daily intraplantar injections of Tyr8-BK (10 nmol/paw) for 7 days caused progressive desensitization (D) of edema in sham-operated and adrenalectomized Wistar rats. DABK (100 nmol/paw) caused marked paw edema in D paws from both groups, which was inhibited by DALBK (100 nmol/paw) and by dexamethasone (0.5mg/kg, s.c.). Systemic injection of lipopolysaccharide (10 micrograms/mouse, 24 h prior) potentiated the first and second phases of Formalin-induced pain but had no effect on paw edema. Coinjection of DABK (2-22 nmol/paw) with low doses of Formalin in lipopolysaccharide-treated mice, which had no effect on naive animals, dose dependently potentiated both phases of Formalin-induced pain but did not modify paw edema. These effects were antagonized by DALBK with ID50 values of 21.9 (first phase) and 64.1 (second phase) nmol/paw. Thus, both progressive desensitization of B2 receptors and systemic treatment with lipopolysaccharide induce a glucocorticoid-sensitive upregulation of B1 receptors mediating paw edema in the rat and Formalin-induced nociception in mice. These results suggest that induction of upregulation of B1 receptors may play important roles in controlling inflammatory processes and hyperalgesia.
 ...
PMID:Expression of B1 kinin receptors mediating paw edema and formalin-induced nociception. Modulation by glucocorticoids. 884 14

We have examined the bradykinin (BK)-stimulated production of prostacyclin (PGI2) by cultured human pulmonary artery smooth muscle cells (HPASMC) pretreated with lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) or interferon gamma (IFN gamma). BK from 0.01 to 1 microM induced a dose-dependent increase in PGI2 production by HPASMC. A striking increase in PGI2 production in response to BK was observed in HPASMC which had been incubated with 1 microgram/ml LPS, 20 U/ml IL-1 beta, 50 U/ml TNF alpha or 100 U/ml IFN gamma. After incubation with various concentrations of LPS or cytokines, the production of PGI2 by BK-stimulated HPASMC showed significant, dose-dependent increases beginning at 0.1 microgram/ml of LPS, 2 U/ml of IL-1 beta and 5 U/ml of TNF alpha, while higher concentrations of IFN gamma failed to cause any further increase in PGI2 production. Our results indicate that BK is a potent agonist to stimulate HPASMC to produce PGI2. LPS, IL-1 beta and TNF alpha effectively enhanced BK-stimulated production of PGI2 by HPASMC, while IFN gamma had only a weak effect on BK-stimulated PGI2 production. Bradykinin-induced enhancement of PGI2 production by LPS, IL-1 beta and TNF alpha might be involved in the regulation of pulmonary vascular tension and prevent a paradoxical thrombogenic effect in endotoxin- or cytokine-mediated inflammation and acute lung injury. These experimental results suggest that vascular smooth muscle cells might actively control the vascular tension and blood supply by producing PGI2 in response to an agonist such as BK.
 ...
PMID:Lipopolysaccharide and cytokines enhance bradykinin-stimulated production of PGI2 by cultured human pulmonary artery smooth muscle cells. 924 8

Neurogenic inflammation implies stimulation of nerves with resultant inflammation in tissue surrounding the nerve terminals. We hypothesized that neurogenic inflammation has a role in cholecystitis. Capsaicin (stimulant of afferent, nociceptive neurons), 6-hydroxydopamine (stimulates release of peptides from sympathetic nerve terminals), bradykinin, lipopolysaccharide, and saline were instilled into guinea pig gallbladders for 24 hr (N = 5 in each group). In parallel, test agents were instilled with 1% Iidocaine. Water transport across gallbladder mucosa, myeloperoxidase and interluekin-1 release from gallbladder tissue, and prostaglandin E2 in luminal fluid were measured. Capsaicin caused water secretion and significant release of myeloperoxidase, interleukin-1, and prostaglandin-E2, effects that were blocked by Iidocaine. 6-Hydroxydopamine did not affect water transport or prostaglandin E2, but did cause myeloperoxidase and interleukin-1 release. Bradykinin- and lipopolysaccharide-induced inflammation were partially inhibited by lidocaine. Taken together, these results suggest that neurogenic inflammation has a role in the pathophysiology of cholecystitis.
 ...
PMID:Neurogenic inflammation in cholecystitis. 924 52


1 2 3 4 Next >>