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)

The present strategy for the prevention of excessive sympathetic neural traffic to the heart relies on the use of beta-blockers, drugs that act at the heart end of the brain-heart axis. In the present study, we attempted to suppress cardiac sympathetic nerve activity by affecting the relevant cardiomotoneurons in the brain using the selective serotonin-1A (5-HT(1A)) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In conscious, unrestrained rabbits, instrumented for recordings of heart rate, arterial pressure, or cardiac output, we provoked increases in cardiac sympathetic activity by psychological (loud sound, pinprick, and air jet) or inflammatory (0.5 microg/kg iv lipopolysaccharide) stresses. Pinprick and air-jet stresses elicited transient increases in heart rate (+50 +/- 7 and +38 +/- 4 beats/min, respectively) and in mean arterial pressure (+16 +/- 2 and +15 +/- 3 mmHg, respectively). Lipopolysaccharide injection caused sustained increases in heart rate (from 210 +/- 3 to 268 +/- 10 beats/min) and in arterial pressure (from 74 +/- 3 to 92 +/- 4 mmHg). Systemically administered 8-OH-DPAT (0.004-0.1 mg/kg) substantially attenuated these responses in a dose-dependent manner. Drug effects were prevented by a selective 5-HT(1A) receptor antagonist, WAY-100635 (0.1 mg/kg iv). Similarly to systemic administration, microinjection of 8-OH-DPAT (500 nl of 10 mM solution) into the medullary raphe-parapyramidal region caused antitachycardic effects during stressful stimulation and during lipopolysaccharide-elicited tachycardia. This is the first demonstration that activation of 5-HT(1A) receptors in the medullary raphe-parapyramidal area causes suppression of neurally mediated cardiovascular changes during acute psychological and immune stresses.
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PMID:Activation of 5-HT1A receptors in the medullary raphe reduces cardiovascular changes elicited by acute psychological and inflammatory stresses in rabbits. 1580 54

The serotonin (5-HT)-3A receptor has been localized in limbic and brainstem structures that regulate hypothalamic--pituitary--adrenal (HPA) activity. We previously showed that 5-HT-3A receptor knock-out (KO) male mice displayed lower ACTH responses to acute restraint or lipopolysaccharide administration compared to age-matched wild-type (WT) males. In the present study, we found that pituitary-adrenal responses to acute stress were not different in female WT and KO mice. Furthermore, we examined the role of the 5-HT-3A receptor in regulation of chronic stress-induced HPA activity in both male and female WT and KO mice. The results show that ACTH, but not corticosterone, responses to novel restraint are lower in chronically cold stressed females compared to non-stressed control females but no effect of 5-HT-3A receptor deletion was observed. In contrast, male mice showed facilitated responses to novel restraint after chronic cold stress and this facilitation produced sex differences in ACTH responses to novel restraint between male and female chronically stressed KO mice. Together, these results indicate that there are sex differences in HPA responses to novel restraint in chronically stressed mice and these differences are partly related to 5-HT-3A receptor function.
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PMID:Pituitary-adrenal activity in acute and chronically stressed male and female mice lacking the 5-HT-3A receptor. 1601 90

Changes in brain tryptophan concentrations may affect the synthesis of brain serotonin (5-hydroxytryptamine, 5-HT). Concentrations of tryptophan are regulated more than those of any other amino acid. Such stimuli as acute stress, carbohydrate ingestion, and treatment with various drugs increase the brain content of tryptophan. Treatment of rats and mice with interleukin-1 (IL-1), interleukin-6 (IL-6), lipopolysaccharide (LPS), and beta-adrenoceptor agonists, as well as a variety of stressors, such as footshock and restraint, all increase brain concentrations of tryptophan. The peak effect following both acute stress and beta-adrenoceptor agonist administration occurs within 30-60 min, whereas the peak effect following LPS and the cytokines occurs much later at around 4-8 h. Experiments using the ganglionic blocker chlorisondamine, and beta-adrenoceptor antagonists suggest that the sympathetic nervous system plays an important role in the modulation of brain tryptophan concentrations. The mechanisms involved in the increases observed in brain tryptophan are discussed, as well as their possible biological significance.
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PMID:Mechanisms and significance of the increased brain uptake of tryptophan. 1636 73

There has been considerable interest in the role of serotonin (5-hydroxytryptamine, 5-HT) in the pathogenesis of pulmonary hypertension due to episodes of primary pulmonary hypertension in humans linked to serotoninergic appetite-suppressant drugs. In this study, we investigated the effect of 5-HT on the development of pulmonary hypertension induced by injecting bacterial lipopolysaccharide (LPS; endotoxin) and cellulose microparticles intravenously, using the nonselective 5-HT(1/2)receptor, antagonist methiothepin. In Experiment 1, broilers selected for ascites susceptibility or resistance under conditions of hypobaric hypoxia were treated with methiothepin or saline, followed by injection of LPS, while recording pulmonary arterial pressure (PAP). In Experiment 2 ascites-susceptible broilers were treated with methiothepin or saline, followed by injection of cellulose microparticles, while recording PAP. In Experiment 3, an i.v. microparticle injection dose shown to cause 50% mortality was injected into ascites-susceptible and ascites-resistant broilers after methiothepin or saline treatment. Injecting methiothepin reduced PAP below baseline values in ascites-susceptible and ascites-resistant broilers, suggesting a role for 5-HT in maintaining the basal tone of the pulmonary vasculature in broilers. Injecting microparticles into the wing vein had no affect on the PAP in the broilers treated with methiothepin, suggesting that 5-HT is an important mediator in the pulmonary hypertensive response of broilers to microparticles. Furthermore, injecting an 50% lethal dose of microparticles into ascites-susceptible and ascites-resistant broilers pretreated with methiothepin resulted in reduced mortality. Serotonin appears to play a less prominent role in the pulmonary hypertensive response of broilers to intravenously injected LPS, indicating that other mediators within the innate response to inflammatory stimuli may also be involved. These results are consistent with our hypothesis that pulmonary hypertension syndrome ensues when vasoconstrictors, such as 5-HT, overwhelm the dilatory effects of vasodilators, such as NO, thereby effectively reducing the pulmonary vascular capacity of pulmonary hypertension syndrome-susceptible broilers.
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PMID:Evaluation of the serotonin receptor blocker methiothepin in broilers injected intravenously with lipopolysaccharide and microparticles. 1713 80

Peripheral administration of bacterial lipopolysaccharide (LPS) elicits anorexia in several species, including rats and mice. There is strong evidence that antagonism of serotonergic activity at 2C receptors (5-HT(2C)R) attenuates LPS anorexia in rats. Here we used pharmacological and genetic approaches to examine the role of the 5-HT(2C)R in LPS anorexia in mice. In Experiment 1, SB 242084, a potent and selective 5-HT(2C) antagonist (0.3 mg/kg) was injected intraperitoneally 15 min before intraperitoneal LPS (2 microg/kg) injections just prior to dark onset in c57BL/6 mice. Food intake was recorded 1, 2 and 4 h after LPS administration. In Experiment 2, we recorded 2, 4 and 24 h food intake following dark onset intraperitoneal LPS (0.125, 0.25, 0.5, 1 and 2 microg/kg) injections in mice with a genetic deletion of 5-HT(2C)R and their WT controls. Our pharmacological results suggest that at least part of the anorexia following peripheral LPS administration is mediated by an increase in 5-HT-ergic activity at the 5-HT(2C)R. Our genetic data, in contrast, suggest that 5-HT(2C)R is not a necessary part of LPS anorexia.
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PMID:Pharmacological, but not genetic, disruptions in 5-HT(2C) receptor function attenuate LPS anorexia in mice. 1730 46

Enhanced bronchial responsiveness during and following lower respiratory tract infections is a major clinical problem, but its pathogenesis is poorly understood. Brain-derived neurotrophic factor (BDNF), which can be released by platelets and leukocytes, has been identified as a mediator of bronchial hyperresponsiveness. It is unknown whether the release of BDNF is altered during lower respiratory tract infections of the adult. In this clinical pilot study, 16 patients (35-80 years old) with the diagnosis of an acute bacterial lower respiratory tract infection and elevated serum concentrations of c-reactive protein (>100 microg/ml) and procalcitonin (>0.1 ng/ml) were examined on admission to the hospital and 1 week after antibiotic treatment. Sixteen age- and sex-matched controls were examined in the same time period. BDNF concentrations in serum and platelets, but not in plasma, were markedly reduced in patients on the day of admission (median <25% of the controls). Analysis of the platelet marker serotonin (5-HT) suggested that the decrease of platelet BDNF is part of a non-specific release of platelet-derived mediators in this condition. Clinical improvement was accompanied by a restoration of serum and platelet BDNF concentrations which returned to control levels after 1 week of treatment. Cell culture experiments revealed that bacterial lipopolysaccharide (LPS) enhanced the release of BDNF by peripheral blood mononuclear cells of the patients at both time points. In conclusion, these data suggest that lower respiratory tract infections might be associated with an augmented release of BDNF by platelets and mononuclear cells.
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PMID:Platelet and plasma BDNF in lower respiratory tract infections of the adult. 1731 33

Monocytes play a critical role in chronic atopic dermatitis (AD) and are the primary leukocytes that interact with activated platelets. Although activated platelets release a variety of mediators, the role of platelets in cutaneous allergic inflammation remains unclear. Serotonin (5-hydroxytryptamine, 5-HT) is one of the prototypic mediators produced by activated platelets. We examined the effect of 5-HT on the function and lifespan of human monocytes. Normal human monocytes treated with 5-HT exhibited upregulated expression of costimulatory molecules, enhanced capacity to produce cytokines following lipopolysaccharide treatment, and to stimulate allogeneic CD4+ T cells. 5-HT also attenuated the apoptosis in normal human monocytes in a dose-dependent manner. The plasma levels of 5-HT were increased in patients with AD compared with controls and correlated with the SCORAD index. 5-HT also inhibited monocyte apoptosis in these patients. 5-HT upregulated Bcl-2 and Mcl-1, and inhibited the activation of caspase-3. The effects of 5-HT on monocyte apoptosis were mediated by the 5-HT1 and/or 5-HT7 receptors. 5-HT and a 5-HT(1/6/7)-receptor agonist induced phosphorylation of extracellular signal-regulated kinase1/2 and activation of nuclear transcription factor-kappaB. These findings support that 5-HT activates monocytes and inhibits apoptosis, allowing them to remain in the tissue and contribute to chronic inflammation.
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PMID:Serotonin activates human monocytes and prevents apoptosis. 1742 35

Exposure to peripheral infections may be permissive to cognitive and behavioral complications in the elderly. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice. Because LPS also causes depressive behavior, the purpose of this study was to determine whether aging is associated with an exacerbated depressive-like response. We confirmed that LPS (0.33 mg/kg intraperitoneal) induced a protracted sickness response in aged mice with reductions in locomotor and feeding activities 24 and 48 h postinjection, when young adults had fully recovered. When submitted to the forced swim test 24 h post-LPS, both young adult and aged mice exhibited an increased duration of immobility. However, when submitted to either the forced swim test or the tail suspension test 72 h post-LPS, an increased duration of immobility was evident only in aged mice. This prolonged depressive-like behavior in aged LPS-treated mice was associated with a more pronounced induction of peripheral and brain indoleamine 2,3-dioxygenase and a markedly higher turnover rate of brain serotonin (as measured by the ratio of 5-hydroxy-indoleacetic acid over 5-hydroxy-tryptamine) compared to young adult mice at 24 post-LPS injection. These results provide the first evidence that age-associated reactivity of the brain cytokine system could play a pathophysiological role in the increased prevalence of depression observed in the elderly.
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PMID:Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system. 1807 91

There has been extensive interest in the role of serotonin (5-hydoxytryptamine, 5-HT) in the pathogenesis of pulmonary hypertension because episodes of pulmonary arterial hypertension in humans have been linked to serotoninergic appetite-suppressant drugs. In this study, we investigated the role of serotonin in the development of pulmonary hypertension induced by intravenously injecting bacterial lipopolysaccharide (LPS, endotoxin) and cellulose microparticles. In experiment 1, we used a 5-HT ELISA kit for the in vitro quantitative determination of 5-HT in plasma during the development of pulmonary hypertension induced by injecting LPS and cellulose microparticles i.v. in broilers. In experiment 2, broilers were either chronically infused with 5-HT via surgically implanted osmotic pumps or received sham surgery as a control. After a period of 10 d, the pulmonary arterial pressure was recorded during challenge with injected LPS or microparticles. Microparticles elicited 5-HT plasma levels more than 2-fold greater than those elicited by LPS from 15 to 45 min postinjection. This indicates that 5-HT is an important mediator in the pulmonary hypertensive response of broilers to microparticles, but may not play a prominent role in the pulmonary hypertensive response to LPS. Furthermore, chronic 5-HT infusion via osmotic pumps caused an increase in the duration of the pulmonary hypertensive response of broilers to microparticles, indicating that the infused 5-HT was sequestered by circulating thrombocytes and then released upon microparticle-mediated thrombocyte activation. Serotonin appears to play a less prominent role in the pulmonary hypertensive response of broilers to LPS, indicating that other mediators within the innate response to inflammatory stimuli may also be involved. These results are consistent with our hypothesis that pulmonary arterial hypertension ensues when vasoconstrictors such as 5-HT overwhelm the dilatory affects of vasodilators such as nitric oxide, thereby effectively reducing the pulmonary vascular capacity of pulmonary arterial hypertension-susceptible broilers.
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PMID:Analysis of plasma serotonin levels and hemodynamic responses following chronic serotonin infusion in broilers challenged with bacterial lipopolysaccharide and microparticles. 1807 60

In the present study, the role of nitric oxide (NO) produced by constitutive and inducible nitric oxide synthases (cNOS and iNOS, resepctively) on the contraction and relaxation of fundus in normal and lipopolysaccharide (LPS)-treated mice was examined. A whole fundic ring isolated from mice pretreated with reserpine was mounted in an organ bath containing Krebs' solution with 0.001 mmol/L atropine. Rings were contracted initially by 5-hydroxytryptamine (5-HT; 0.03 mmol/L) before relaxation was induced using ATP (0.03 mmol/L), ADP (0.03 mmol/L), pentoxifylline (0.002 mmol/L), electrical field stimulation (EFS; 50 V, 1 msec, 50 Hz, 3 min) and L-arginine (0.05 mmol/L). All drugs and EFS induced significant relaxation of isolated rings. The relaxations induced were significantly inhibited by N(G)-nitro-L-arginine methyl ester (L-NAME; 1.0 mmol/L). However, the iNOS inhibitors L-N(6)-(1-iminoethyl) lysine hydrochloride (L-NIL; 1.0 mmol/L) and amino guanidine (AMG; 1.0 mmol/L) had no significant effect on tissue relaxation. Then, the relaxant effects of 0.03 mmol/L ATP were tested on precontracted isolated fundic rings taken from 10 mg/kg LPS-treated animals. The non-selective NOS inhibitor L-NAME (10 mg/kg), the iNOS inhibitors L-NIL (3 mg/kg) and AMG (20 mg/kg) and betamethasone (0.1 mg/kg) were used to examine the role of NO produced by iNOS in the relaxation responses. It was found that the level of contraction induced by 0.03 mmol/L 5-HT in rings isolated from LPS-treated animals was significantly (P < 0.5) less than that in rings from untreated mice. However, precontracted tissues from LPS-treated mice were significantly relaxed by ATP and the relaxation response to ATP was significantly inhibited by L-NIL, ANG and betamethasone, but not by L-NAME. We suggest that, in LPS-treated mice, the production of NO from iNOS produces a reduction in the contractile response, as well as a decrease in NO formation by cNOS, resulting in changes to smooth muscle cell function.
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PMID:Role of nitric oxide produced by constitutive and inducible nitric oxide synthases in the mouse gastric fundus. 1850 51


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