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

Alterations in regional brain concentration of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their metabolites were investigated in male BALB/c mice injected intraperitoneally with bacterial lipopolysaccharide (LPS, 2 mg kg(-1)) or recombinant murine tumor necrosis factor alpha (TNFalpha, 0.1 mg kg(-1)) at 2, 6, 12 and 24 h after the injection. At 2 h post-injection the LPS administration resulted in hypothermia, which was not apparent at later time points. No consistent effects were observed by either LPS or TNFalpha on peripheral leukocyte counts or plasma transaminase levels. Both LPS and TNFalpha slightly elevated NE metabolism in the striatum at 2-12 h. Concentrations of DA and its metabolites were significantly elevated only in the hypothalamus following TNFalpha at 24 h. Tumor necrosis factor alpha exerted pronounced effects on 5-HT metabolism in most brain regions at 2 h. Results suggest that the effect of LPS is more complex compared with TNFalpha because of the endogenous production of other cytokines including the TNFalpha.
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PMID:Effects of endotoxin and tumor necrosis factor alpha on regional brain neurotransmitters in mice. 1094 81

Previous studies suggested that peripheral immune mediators may involve intermediates acting on the vagus nerve, such as CCK or serotonin (5-HT). We have therefore investigated a possible role for vagal CCK-A and 5-HT(3) receptors in the febrile response after intraperitoneal human recombinant interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS). Unanesthetized, adult male rats instrumented with abdominal thermistors were given intraperitoneal CCK-8 sulfate (100 or 150 microgram/kg) or 2-methyl-5-hydroxytryptamine maleate (4 mg/kg). In other experiments, rats were treated with either antagonists to the 5-HT(3) receptor (ondansetron HCl; 100 microgram/kg) or the CCK-A receptor (L-364,718, 100 or 200 microgram/kg) in combination with LPS or IL-1beta. CCK administration caused a short-lived hypothermia, but interference with the action of endogenous CCK at CCK-A receptors was without effect on IL-1beta- or LPS-induced fever. Neither activation of 5-HT(3) receptors nor blockade of 5-HT(3) receptors affected body temperature or LPS fever. Taken together, our data support the idea that vagal afferents responsive to pyrogenic cytokines may be different from those responsive to CCK or 5-HT.
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PMID:Vagal CCK and 5-HT(3) receptors are unlikely to mediate LPS or IL-1beta-induced fever. 1095 54

Serotonin (5-HT) up-regulates B and T lymphocyte proliferation by activating mitogen-induced cell surface 5-HT(1A) receptors. The mechanism of 5-HT(1A) receptor induction by B and T cell mitogens at the mRNA and protein levels in mouse splenocytes was addressed. Quantitation by RNase protection assay showed maximal increases of 3.4-, 3.0-, 3.8-, and 4.9-fold in relative 5-HT(1A) mRNA levels after 48 h of stimulation of splenocytes with lipopolysaccharide, phytohemagglutinin, concanavalin A, or phorbol 12-myristate 13-acetate plus ionomycin, respectively, as compared with unstimulated cells. Mitogens did not alter 5-HT(1A) mRNA stability (t(12) = 26 h), but induction of 5-HT(1A) mRNA was blocked by the transcriptional inhibitor actinomycin D (10 microgram/ml) and by inhibition of nuclear factor-kappaB signaling. Additionally, mitogenic stimulation of transcription was paralleled by increased cell surface 5-HT(1A) receptor immunoreactivity in splenocytes. Thus, mitogen-induced 5-HT(1A) receptor expression appears to involve transcriptional regulation by the nuclear factor-kappaB signaling cascade. Increased expression of the 5-HT(1A) receptor in activated B and T lymphocytes may enhance the immune response and provide therapeutic target for tissue inflammation and immune stimulation.
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PMID:Transcriptional mechanisms for induction of 5-HT1A receptor mRNA and protein in activated B and T lymphocytes. 1108 Apr 94

1. Several reports have shown that serotonin (5-HT)2A receptor density and its function are altered after physiological or pharmacological stress. To examine whether an acute administration of lipopolysaccharide (LPS), a bacterial endotoxin, affected 5-HT2A receptor function, wet dog shakes of male Wistar rats were observed after a subcutaneous injection of DOI, a 5-HT2A receptor agonist following LPS treatment. Body weight change and locomotor activity were also observed. 2. DOI (1 mg/kg)-induced WDS significantly decreased after 400 or 1000 microg/kg LPS treatment compared with that of control rats 1 and 3 hr after injection, and WDS completely recovered 8 hr after LPS treatment. Treatment with 10 mg/kg indomethacin (IND) or 1 mg/kg naltrexone (NLTX) canceled the effect of 400 microg/kg LPS on DOI-induced WDS. 3. Body weight decrease was significantly greater in LPS-treated rats compared with control rats 3, 5 and 8 hr after treatment. Treatment with IND (10 mg/kg) significantly recovered the reduction in body weight induced by 400 microg/kg LPS. Treatment with NLTX (1 mg/kg) also prevented the LPS effect on body weight decrease. 4. Eight hr after treatment with LPS (400 microg/kg), the rats showed significant attenuation of locomotor activity. IND (10 mg/kg) treatment abolished the inhibitory effect of LPS on locomotor activity, and NLTX (1 mg/kg) also improved the decrease in locomotion 8 hr after LPS treatment. 5. Plasma tumor necrosis factor (TNF)-alpha concentration dramatically increased 1 hr after the injection of 400 microg/kg LPS, and returned almost to the basal level 3 hr later. Next, rats were injected with 50 microg/kg TNF-alpha intraperitoneally, and body weight change and DOI-induced WDS was determined 3 hr after TNF-alpha injection. Body weight loss was significantly greater in rats treated with TNF-alpha. On the other hand, DOI-induced WDS was not altered when rats were treated with TNF-alpha. 6. These results suggest that acute treatment with LPS inhibited 5-HT2A receptor-mediated behavior via cyclooxygenase and opioid receptor activation, but that the inhibition of the WDS by LPS appears to be independent of TNF-alpha production.
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PMID:Effect of acute lipopolysaccharide administration on (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane-induced wet dog shake behavior in rats: comparison with body weight change and locomotor activity. 1129 84

Interactions between monoaminergic neurochemistry and macronutrient intake have been frequently shown. Because monoaminergic systems in the brain are also closely involved in behavioral and physiological stress responses it can be hypothesized that differences in the macronutrient composition of diets are reflected in these responses. The present studies, therefore, were designed to assess the consequences of a change in dietary macronutrient composition on a variety of physiological and behavioral responses (both acute and long-term) to a number of stressors. The effect of chronic high-fat (HF; 61% kcal from fat) feeding on the stress responses was compared with controls receiving regular high-carbohydrate (HC; 63% kcal from carbohydrates) laboratory chow. Rats were kept on this diet for at least 2 months before they were exposed to either psychological (social defeat) or physiological (lipopolysaccharide, LPS, administration) stress. At baseline, chronic HF feeding caused a slight, but significantly reduction in body temperature relative to that observed in HC-fed rats. Following social defeat or LPS injection, HF feeding caused a faster recovery of the body temperature increase relative to animals on the HC diet. Stress-induced suppression of home cage locomotor activity and body weight gain were also reduced by HF feeding. The serotonergic 5-HT(1a) receptor hyposensitivity that was observed in HC-fed rats 2 weeks after stress was absent in the HF regimen. Although the present results cannot be readily interpreted as showing purely beneficial effects of high-fat diets on stress responsivity, the findings in the present study do encourage further investigation of possible ameliorating effects of high-fat diets on aspects of the behavioral and physiological response stress.
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PMID:Behavioral and physiological responses to stress are affected by high-fat feeding in male rats. 1143 64

The present study examined the effect of systemic administration of lipopolysaccharide (LPS; 100 and 250 microg/kg, i.p.) on tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) activities in frontal cortex, striatum and midbrain of the rat. Enzyme activities were determined by measuring accumulation of the transient intermediates 5-hydroxytrptophan (5-HTP) and L-dihydroxyphenylalanine (L-DOPA) following in vivo administration of the decarboxylase inhibitor, NSD 1015. TPH activity was increased 2 hours after administration of LPS (100 and 250 microg/kg) in both frontal cortex and midbrain, and a secondary increase was seen in the midbrain 12 hours after challenge. LPS provoked an increase in TH activity in the midbrain only, and this was evident for up to 24 hours after LPS administration. Thus in addition to previous studies demonstrating that LPS increases in vivo NA, DA and 5-HT release, this study shows that LPS increases the activity of the rate-limiting enzymes responsible for their synthesis.
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PMID:Lipopolysaccharide administration produces time-dependent and region-specific alterations in tryptophan and tyrosine hydroxylase activities in rat brain. 1145 92

As part of our characterization of the developmental consequences of prenatal cocaine exposure, cocaine was injected into eggs containing viable chicken embryos on embryonic day (E) 18 and the fever response to the endotoxin lipopolysaccharide (LPS) and a delayed-type hypersensitivity response to phytohemagglutinin (PHA) were assessed postnatally. E18 cocaine exposure did not affect basal body temperature. LPS induced a fever in the chicks at 4 h post-injection on post-hatch day (D) 4 and 2 h post-injection on D24. E18 cocaine exposure suppressed the peak LPS-induced fever by 50% at both ages. E18 cocaine exposure also suppressed the hypersensitivity reaction to an intradermal injection of PHA on D17, while having no effect on the response to a saline injection. To determine the importance of serotonin(2) (5-HT(2)) receptors in the developmental toxicity of cocaine, varying doses of the 5-HT(2) antagonist ritanserin were injected on E17 followed by cocaine on E18. Ritanserin, like cocaine, did not alter basal temperature, but it dose-relatedly attenuated or blocked cocaine's effect on LPS-induced fever on both D4 and D24. Ritanserin pretreatment was also able to block the blunted isolation stress response seen in D16 chicks following E18 cocaine exposure. Thus, late prenatal cocaine exposure significantly alters adaptive fever and hypersensitivity responses, and embryonic 5-HT(2) receptors played a mediating role in the fever effect.
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PMID:Embryonic "binge" cocaine exposure alters neural-immune and neural-endocrine interactions in young chickens: involvement of serotonin(2) receptors. 1155 98

The present study was designed in order to clarify the mechanisms of diminished phosphoinositide (PI) hydrolysis by lipopolysaccharide (LPS) in blood vessels. In vitro pretreatment of rat aortic strips with LPS (1 microg/ml) for 10 or 24 hrs inhibited 5-hydroxytryptamine (5-HT, 100 microM)-induced inositol monophosphate accumulation in a time-dependent manner. Coincubation of the aortas with N(G)-monomethyl-L-arginine (LNMMA, 1 mM) completely prevented the early diminution of 5-HT-stimulated PI hydrolysis after 10-hr exposure to LPS but did not affect the delayed diminution after 24-hr exposure. Coincubation with cycloheximide (1 microM) did not prevent the delayed LPS-induced diminution of phosphoinositide hydrolysis. Tetraethylammonium (10 mM) did not restore the diminished phosphoinositide hydrolysis after 24-hr exposure to LPS, suggesting that the diminution is not due to K+ channel activation. Sodium fluoride (10 mM)-induced inositol monophosphate accumulation was also decreased in the aortic strips after LPS incubation for 24 hrs, and this decrease was not prevented by coincubation with LNMMA. LPS incubation time-dependently increased nitric oxide (NO) production in the aortas, which was completely inhibited by LNMMA or cycloheximide. These results suggest that NO is mainly involved in the inhibitory action of LPS on stimulated-PI hydrolysis in the early stage, while in the later stage, a factor(s) besides NO causes attenuation of the stimulated-PI hydrolysis.
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PMID:Nitric oxide-dependent and -independent inhibition by lipopolysaccharide of phosphoinositide hydrolysis in vascular smooth muscle. 1172 88

Inflammation and neuronal degeneration of the substantia nigra (SN) occur in Parkinson's disease (PD). We studied the effects of intranigral lipopolysaccharide (LPS) injection on adult Sprague-Dawley rats. Locomotor activity measurement, neurotransmitter determination and perfusion fixation for immunohistochemistry were done on the 7th day. Bilateral LPS injection increased locomotor activity 2- to 3-fold. In the SN, dopamine (DA) and serotonin (5-HT) decreased but the ratios dihydroxyphenylacetic acid (DOPAC)/DA, homovanillic acid (HVA)/DA and 5-hydroxyindole-acetic acid (5-HIAA)/5-HT increased. In the striatum, DA, DOPAC, HVA, 3-methoxytyramine and epinephrine decreased but HVA/DA and 5-HIAA/5HT ratios increased. Unilateral LPS decreased dopamineric neurons ipsilaterally but increased contralaterally. This study provides the first evidence of behavioral hyperactivity, epinephrine suppression and neuronal plasticity in the LPS model of PD.
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PMID:Behavior, neurochemistry and histology after intranigral lipopolysaccharide injection. 1193 Jan 22

Inflammatory bladder disorders such as interstitial cystitis (IC) deserve attention since a major problem of the disease is diagnosis. IC affects millions of women and is characterized by severe pain, increased frequency of micturition, and chronic inflammation. Characterizing the molecular fingerprint (gene profile) of IC will help elucidate the mechanisms involved and suggest further approaches for therapeutic intervention. Therefore, in the present study we used established animal models of cystitis to determine the time course of bladder inflammatory responses to antigen, Escherichia coli lipopolysaccharide (LPS), and substance P (SP) by morphological analysis and cDNA microarrays. The specific aim of the present study was to compare bladder inflammatory responses to antigen, LPS, and SP by morphological analysis and cDNA microarray profiling to determine whether bladder responses to inflammation elicit a specific universal gene expression response regardless of the stimulating agent. During acute bladder inflammation, there was a predominant infiltrate of polymorphonuclear neutrophils into the bladder. Time-course studies identified early, intermediate, and late genes that were commonly up-regulated by all three stimuli. These genes included: phosphodiesterase 1C, cAMP-dependent protein kinase, iNOS, beta-NGF, proenkephalin B and orphanin, corticotrophin-releasing factor (CRF) R, estrogen R, PAI2, and protease inhibitor 17, NFkB p105, c-fos, fos-B, basic transcription factors, and cytoskeleton and motility proteins. Another cluster indicated genes that were commonly down-regulated by all three stimuli and included HSF2, NF-kappa B p65, ICE, IGF-II and FGF-7, MMP2, MMP14, and presenilin 2. Furthermore, we determined gene profiles that identify the transition between acute and chronic inflammation. During chronic inflammation, the urinary bladder presented a predominance of monocyte/macrophage infiltrate and a concomitant increase in the expression of the following genes: 5-HT 1c, 5-HTR7, beta 2 adrenergic receptor, c-Fgr, collagen 10 alpha 1, mast cell factor, melanocyte-specific gene 2, neural cell adhesion molecule 2, potassium inwardly-rectifying channel, prostaglandin F receptor, and RXR-beta cis-11-retinoic acid receptor. We conclude that microarray analysis of genes expressed in the bladder during experimental inflammation may be predictive of outcome. Further characterization of the inflammation-induced gene expression profiles obtained here may identify novel biomarkers and shed light into the etiology of cystitis.
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PMID:Gene expression profiling of mouse bladder inflammatory responses to LPS, substance P, and antigen-stimulation. 1205 14


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