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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of intravenous injection of 10 micrograms of a lipopolysaccharide (endotoxin) extracted from E. coli to rabbits on the responses of isolated lingual arteries to des-Arg9-bradykinin (a specific kinins B1-receptor agonist) was studied. Endotoxin injection led to the appearance of the endothelium-independent contractile effect of des-Arg9-bradykinin in the arteries; endotoxin elicited this response when administered at 1, 5 or 20 hr before the experiment, in a time-interval dependent manner. The contractile response to des-Arg9-bradykinin of the arteries isolated from animals receiving endotoxin 20 hr before the experiment was attenuated by des-Arg9-[Leu8]-bradykinin (a specific inhibitor of kinins B1-receptor) or pretreatment of the animals with an inhibitor of protein synthesis (cycloheximide and actinomycin D). When compared with the effect of des-Arg9-bradykinin, bradykinin (a potent kinin B2-receptor, but weak B1-receptor stimulant) caused slight contraction of the arteries; however, this effect was not endotoxin-dependent and was not modified by des-Arg9-[Leu8]-bradykinin. Effect of in vitro preincubation with endotoxin of the arteries isolated from animals receiving saline 20 hr before the experiment was further studied. The preincubation (for 1 and 5 hr) with endotoxin of the arteries in the presence or absence of plasma had no effect on the sensitivity of the arteries to des-Arg9-bradykinin; the sensitivity was also unaffected in the presence or absence of endotoxin, thus suggesting that there is no interaction between endotoxin and some plasma-related factors with the appearance of the contraction in response to the kinin B1-receptor agonist in the arteries in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The contractile response of isolated lingual arteries from rabbits treated with bacterial lipopolysaccharide via the stimulation of B1-receptors for kinins]. 191 44

Microvascular endothelial cells from the adult rat brain were cultured on Matrigel and found to express many differentiated properties including secretion of prostacyclin (PGI2) and von Willebrand's factor (vWF). Brain microvascular endothelial cells (BMECs) were purified by dextran and percoll gradients after enzymatic treatment and cultured under various conditions. BMECs that were plated on Matrigel stained positively for factor VIII-related antigen and incorporated Di-I-acetylated low density lipoprotein, whereas BMEC plated on fibronectin, gelatin, or uncoated dishes did not express any of the above properties which are characteristic of endothelial cells. vWF was measured by a sensitive ELISA in the culture media of BMECs plated on different types of matrices. Specificity of the anti-human vWF antibodies for the rat vWF was verified by immunoabsorption on a solid phase, sodium dodecyl sulfate, and Western blot analysis. BMECs also secreted vWF into the culture media only when the cells were plated on Matrigel, and this secretion was augmented after a 6 h incubation with an interleukin-1 tumor necrosis factor-alpha mixture, but not by lipopolysaccharide. From different matrices tested, only Matrigel permitted the secretion of PGI2 by BMECs. Cells also proved to be sensitive to mechanical stimulation and became refractory to secretagogue if the mechanical stimulation was serially repeated. Under the best conditions, stimulation of the cells with bradykinin (1 microM) substantially increased PGI2 secretion. These data indicate that growth of BMECs on Matrigel in vitro permits the expression of classical endothelial cell markers in a manner similar to the behavior of these cells in situ.
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PMID:Extracellular matrix permits the expression of von Willebrand's factor, uptake of di-I-acetylated low density lipoprotein and secretion of prostacyclin in cultures of endothelial cells from rat brain microvessels. 191 89

The role of membrane potential (Em) on the initiation of DNA synthesis in murine macrophage cell line PU5-1.8 was investigated with fluorescent probes bis-oxonol and diS-C3-(5). Incubation of PU5-1.8 cells in high K(+)-HEPES buffer or with gramicidin at 37 degrees C for 1h that depolarized the membrane induced [3H]-thymidine incorporation and expression of early response gene such as c-myc and c-fos. When PU5-1.8 cells were treated with a number of agents including fetal calf serum (FCS), lipopolysaccharide (LPS), epidermal growth factor (EGF), N-formyl-methionyl-leucyl-phenylalanine (FMLP) and bradykinin (BK), only FCS caused DNA synthesis and membrane depolarization. Other agents had no effect on these events. The FCS-mediated DNA synthesis in PU5-1.8 cells was inhibited by clamping the membrane potential with valinomycin. Moreover, intracellular alkalinization induced by nigericin at pH 7.9, which is believed to be a permissive signal for mitogenesis, caused membrane depolarization. On the other hand, challenge of cells with phorbol 12-myristate 13 acetate (PMA) suppressed the K(+)-mediated DNA synthesis. However, the treatment of cells with PMA did not change the membrane potential but suppressed the gramicidin-mediated membrane depolarization. These observations suggest that there is a correlation between membrane depolarization and initiation of DNA synthesis in PU5-1.8 cells. PKC may be acting as a modulator in this transducing pathway.
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PMID:Membrane depolarization was required to induce DNA synthesis in murine macrophage cell line PU5-1.8. 194 52

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.
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PMID:Nitrate biosynthesis in rats, ferrets and humans. Precursor studies with L-arginine. 233 12

The dose and time dependence of endotoxin-induced activation of the plasma contact system have been studied. Citrated pool plasma was incubated at 37 degrees C with endotoxin doses of 2.10(5), 2.10(6), 2.10(7), and 2.10(9) ng/l (lipopolysaccharide B, E. coli 026: B6, Difco Laboratories, Detroit, MI) for 24 hr. Samples for determination of components of the contact system were obtained prior to incubation and at 1, 2, 4, 6, 12, and 24 hr. Plasma kallikrein (KK) activity markedly increased at 12 hr in test plasma containing the highest dose of endotoxin (2.10(9) ng/l). Coincident with the elevated KK activity, reductions of both plasma prekallikrein (PKK) and functional kallikrein inhibition (KKI) were seen as assayed by chromogenic peptide substrate analyses. Also, functionally determined alpha 2-macroglobulin (alpha 2-M) and C1 inhibitor (C1INH) values were decreased, confirming the reduction of KKI values. Changes of Hageman factor (FXII), PKK, and high molecular weight kininogen (HMWK) values were also found at the same time point when assayed by immunochemical techniques. The same pattern of changes was seen in test plasma containing 2.10(7) and 2.10(6) ng/l of endotoxin. These changes, however, were less pronounced and not seen until 24 hr after beginning incubation. In control plasma and in plasma containing the lowest dose of endotoxin (2.10(5) ng/l), no changes were seen in any factors of the contact system. Our study shows that in vitro endotoxin-induced activation of the contact system is a slow process that is both time and dose dependent.
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PMID:Dose dependence of endotoxin-induced activation of the plasma contact system: an in vitro study. 246 83

The effect of the selective kinin B1 receptor agonist des-Arg9-BK was studied on blood pressure and on the in vitro aorta of rabbits pretreated 18 h earlier with lipopolysaccharide from E. coli, an infusion of bradykinin or with one of three angiotensin converting enzyme inhibitors captopril, enalapril or teprotide. The hypotensive response in vivo and contractile response seen on the in vitro aorta was selectively increased to des-Arg9-BK in all pretreated groups compared to controls, effects which were blocked by the selective competitive kinin B1 receptor antagonist des-Arg9-[Leu8]BK. Dexamethasone given to lipopolysaccharide pretreated rabbits had no effect on the increased hypotensive response seen with des-Arg9-BK. The skin vascular permeability response to des-Arg9-BK, bradykinin and histamine remained unchanged in the groups pretreated with lipopolysaccharide or captopril compared to controls. The possible mechanism(s) whereby angiotensin converting enzyme inhibitors produce this effect and the possible relevance to the inflammatory side-effects seen with this group of drugs is discussed.
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PMID:Angiotensin converting enzyme inhibitors and expression of des-Arg9-BK (kinin B1) receptors in vivo. 254 Sep 86

Phorbol esters are known to alter microfilaments but it is not clear if the changes correspond to modulation of the phosphoinositide turnover/protein kinase C system. The novel technique of laser scanning confocal epifluorescence was used to study fiber orientation in phorbol ester treated cells. We treated endothelial cells with control agents and agents known to stimulate protein kinase C: 4 alpha-phorbol, phorbol 12-myristate 13-acetate (PMA), phorbol dibutyrate (PDB), or lipopolysaccharide. After incubation with the test agents, the endothelial cell microfilaments were stained with rhodamine pholloidin and viewed by conventional epifluorescence and by laser scanning confocal epifluorescence microscopy. The images obtained by the confocal microscopy corresponded to a thin optical section through the cells, 300 nm or more in thickness. The microfilaments extended predominantly in the plane of focus. After exposure of the cells to phorbol esters, the stress fibers became more nearly parallel in arrangement or were shortened, but remained in the plane of focus. The modification of microfilaments in response to phorbol esters was quantitated by a single blind analysis. In order to compare the morphological changes with a biochemical action of the phorbol esters, we measured phosphoinositide turnover. The dose-dependence of morphological changes was compared and contrasted to the dose-dependent effect of phorbol esters on bradykinin-stimulated phosphoinositide turnover. PMA had about the same EC50 (1-5 nM) for both biochemical and morphological processes. PDB was less potent in inducing the disruption of microfilament structure than in inhibiting phosphoinositide turnover. Lipopolysaccharide was ineffective in inducing a morphological change under these conditions. A simple activation of protein kinase C is insufficient to explain the dose-dependent effects of phorbol esters. Thus a morphometric analysis can help distinguish the potency of cytoskeleton modulators.
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PMID:Effects of phorbol esters on endothelial cell microfilaments: laser scanning confocal microscopy and quantitative morphometry of dose dependent changes. 262 64

The selective competitive bradykinin (BK) antagonist (B4148) produced significant inhibition of the hypotensive effect of BK in rats. Using a rat model of endotoxin shock, the fall in mean arterial blood pressure to an intravenous injection of lipopolysaccharide from E. coli was significantly attenuated by the B4148 as compared to controls. These findings suggest that kinins are involved in the hypotensive response to endotoxin shock in rats. The development of potent BK antagonists offers a new experimental approach for evaluating the role of kinins in this and other disease states.
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PMID:Endotoxin shock in the rat: reduction of arterial blood pressure fall by the bradykinin antagonist B4148. 267 79

The kallikrein-kinin system is activated during endotoxic shock, suggesting that bradykinin plays a role in the pathology of this disease. To test this hypothesis, a bradykinin antagonist, D-Arg-Hyp3-D-Phe7-bradykinin (NPC 567), was studied in conscious, chronically catheterized rats undergoing lipopolysaccharide (LPS)-induced endotoxic shock. LPS treatment resulted in an increase in circulating bradykinin from less than 23 pg/ml to 144 +/- 18 pg/ml at 1 hr. Intravenous administration of LPS resulted in a 38% drop in mean arterial pressure at 1 hr which was partially reversed by NPC 567. NPC 567 did not affect the moderate tachycardia observed following LPS. NPC 567 infusion at 8 nmol/kg/min dramatically reduced mortality from 100% to 50% at 24 hr (P less than 0.01). In response to LPS, blood thromboxane B2 (TXB2) rose from less than 200 pg/ml to 2,298 +/- 64 pg/ml, while 6-keto-prostaglandin-F1 alpha (6kPGF1 alpha) rose from 289 +/- 23 pg/ml to 7,927 +/- 822 pg/ml. NPC 567 reduced the rise in 6kPGF1 alpha by 42% (P less than 0.05), without affecting TXB2. In summary, NPC 567 reduced mortality in rats treated with LPS, reduced the rise in 6kPGF1 alpha and partially reversed the hypotensive effects. These results suggest that bradykinin plays a significant role in the pathology of endotoxic shock.
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PMID:D-Arg-[Hyp3-D-Phe7]-bradykinin, a bradykinin antagonist, reduces mortality in a rat model of endotoxic shock. 270 51

Des-Arg9-bradykinin (BK) is a selective agonist of the B1 type receptors for kinins. The biological responses to des-Arg9-BK are known to be selectively up-regulated following some types of tissue injury. Two models using rabbits were previously characterized. Firstly, in vivo, lipopolysaccharide (LPS) induces a state of sensitivity to des-Arg9-BK, which becomes a hypotensive peptide. Pretreatment of rabbits with dexamethasone sodium phosphate (DEX) did not modify the induction of cardiovascular sensitivity by LPS. Secondly, isolated rabbit aortic strips incubated in vitro exhibit a spontaneous, time-dependent increase in their responsiveness to des-Arg9-BK. This up-regulation process is selectively inhibited by DEX and stimulated by LPS applied in vitro. DEX application prevented the stimulant effect of LPS in vitro. A variety of growth factors and interleukins as well as interferon-gamma, serotonin, bradykinin and the metalloprotease inhibitor 2-mercaptoethanol were ineffective in modulating the spontaneous up-regulation of contractile responses to des-Arg9-BK. Of the known substances which do modulate this system, only epidermal growth factor (EGF) enhanced aortic contractions to des-Arg9-BK following an acute (15 min) exposure near the end of the 6-hour incubation period used in these studies. The possible involvement of des-Arg9-BK and related peptides in immunopathology is discussed.
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PMID:Pharmacological modulation of the up-regulated responses to des-Arg9-bradykinin in vivo and in vitro. 278 31


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