Cysteinyl-Leukotriene Levels in Intracerebral Hemorrhage:An Edema-Promoting Factor?

Winking, Michael; Deinsberger, W.; Joedicke, A.; Boeker, D. K.

doi:10.1159/000015874

Cited by 15 publications

(18 citation statements)

References 30 publications

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“…2 Tissues other than myeloid cell containing organs, such as the spleen and lymph nodes, that showed expression of the mRNA for the CysLT 2 receptor included regions of the central nervous system, the adrenal gland, and the heart. The synthesis and activities of cysteinyl leukotrienes in the brain of various animal species has been well documented (21)(22)(23). Studies on expression of both the CysLT 1 and CysLT 2 receptors in the central nervous system are under way in our laboratories.…”

Section: Human Tissue Rna Northern Blot and In Situ Analyses-mentioning

confidence: 99%

Characterization of the Human Cysteinyl Leukotriene 2 Receptor

Heise¹,

O’Dowd²,

Figueroa³

et al. 2000

Journal of Biological Chemistry

599

673

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Section: Human Tissue Rna Northern Blot and In Situ Analyses-mentioning

confidence: 99%

Characterization of the Human Cysteinyl Leukotriene 2 Receptor

Heise¹,

O’Dowd²,

Figueroa³

et al. 2000

Journal of Biological Chemistry

599

673

View full text Add to dashboard Cite

“…This suggests the existence of some subtype of the CysLT receptor. CysLT production has also been reported to increase in the cerebrospinal fluid in some disease states such as multiple sclerosis [130] and intracerebral hemorrhage which causes impairment of the bloodbrain barrier and finally neuronal edema and death [131] .…”

Section: Neuroendocrine Effectsmentioning

confidence: 99%

Cysteinyl Leukotrienes and Their Receptors: Molecular and Functional Characteristics

Singh¹,

Gupta²,

Dastidar³

et al. 2010

Pharmacology

184

143

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The cysteinyl leukotrienes (CysLTs) are a family of potent inflammatory lipid mediators synthesized from arachidonic acid by a variety of cells including mast cells, eosinophils, basophils and macrophages. The family includes leukotriene C₄ (LTC₄), leukotriene D₄ (LTD₄) and leukotriene E₄ (LTE₄), which are potent biological mediators in the pathophysiology of inflammatory diseases and trigger contractile and inflammatory processes through the specific interaction with cell surface receptors, belonging to the superfamily of G-protein-coupled receptor. Pharmacological characterizations have suggested the existence of at least 2 types of CysLT receptors based on potency of agonist and antagonist, designated as CysLT₁ and CysLT₂. The CysLT₁ receptors are mostly expressed in lung smooth muscle cells, interstitial lung macrophages and the spleen, and it has been studied a lot elucidating its role in the etiology of airway inflammation and asthma. On the other hand, CysLT₂ receptors are present in the heart, brain and adrenal glands. This review discusses the role of CysLTs and their receptor in the pathophysiology of various inflammatory disorders. The understanding of CysLTs and their receptors in allergic airway disease is currently limited to CysLT₁-receptor-mediated effects, and the role of the CysLT₂ receptors is pharmacologically less well defined, as there is no specific antagonist available yet. Specific CysLT₂-receptor-selective antagonists would be very helpful to identify the precise role of CysLT and their receptors. Some recent evidence indicates the existence of additional receptor subtypes and requires further investigation for a better understanding of the role of the CysLT receptors. This review is an effort to summarize the localization, regulation and expression pattern along with the molecular and functional pharmacology of the CysLT receptors and to discuss their role in the pathophysiology of different diseases along with the recent update.

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“…Cysteinyl leukotrienes (CysLTs) production was consistently increased in cerebrospinal fluid in patients with multiple sclerosis (51) or intracerebral hemorrhage (60) as well as in brain tumors (54).…”

mentioning

confidence: 99%

P2Y₁and Cysteinyl Leukotriene Receptors Mediate Purine and Cysteinyl Leukotriene Co-Release in Primary Cultures of Rat Microglia

Ballerini

Iorio

Ciccarelli

et al. 2005

Int J Immunopathol Pharmacol

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Inflammation is widely recognized as contributing to the pathology of acute and chronic neurodegenerative conditions. Microglial cells are pathologic sensors in the brain and activated microglia have been viewed as detrimental. Leukotriene, including cysteinylleukotrienes (CysLTs) are suggested to be involved in brain inftammation and neurological diseases andATP, by its receptors is a candidate for microglia activation.A23187 (l0f1M) stimulated microglia to co-release CysLTs and [3H]adenine based purines ([3H]ABPs), mainly ATP. The biosynthetic production of CysLTs was abolished by 10f1MMK-886, an inhibitor of 5-lipoxygenase-activating protein activity. RT-PCR analysis showed that microglia expressed both CysLT I / CysLT 2 receptors, P 2Y1 ATPreceptors and several members of the ATP binding cassette (ABC) transporters including MRP1, MRP4 and Pgpo The increase in [Ca 2+]i elicited by LTD4 (0.1 f1M) and 2MeSATP (l00J.1M), agonists for CysLT-and P 2Y1 -receptors, was abolished by the respective antagonists, BAYu9773 (0.5 f1M) and suramin (50 f1M). The stimulation of both receptor subtypes, induced a concomitant increase in the release of both [3H]ABPs and CysLTs that was blocked by the antagonists and significantly reduced by a cocktail ofABC transporter inhibitors, BAPTAIAM (intracellular Ca2+ chelator) and staurosporine (0.1 f1M, PKC blocker). P2Y antagonist was unable to antagonise the effects ofLTD 4 and BAYu9773 did not reduce the effects of2MeSATP. These data suggest that: i) the efffux of purines and cysteinyl-leukotrienes is specifically and independently controlled by the two receptor types, ii) calcium, PKC and the ABC transporter system can reasonably be considered common mechanisms underlying the release ofABPs and CysLTs from microglia. The blockade ofP 2Y1 orCysLT/CysLT 2 receptors by specific antagonists that abolished the raise in [Ca"]! and drastically reduced the concomitant efffux of both compounds, as well as the effects ofBAPTA and staurosporine support this hypothesis. In conclusion, the data of the present study suggest a cross talk between the purine and leukotriene systems in a possible autocrine/paracrine control ofthe microglia-mediated initiation and progression of an inftammatory response.Proinflammatory products of 5-lipoxygenase (5-LO) pathway, including cysteinylleukotrienes (LTC4, LTD4, LTE4) are suggested to be involved in brain inflammation and neurological diseases. In aging brain and in Alzheimer's disease an increase in the activity of 5-LO has been shown (41, 57). The inhibition of the enzyme or 5-LO activating protein (FLAP) reduced the microglia-mediated toxicity towards neuronal cells, whereas the toxicity was enhanced by the cysteinyl leukotriene LTD4 (35).

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Cysteinyl-Leukotriene Levels in Intracerebral Hemorrhage:An Edema-Promoting Factor?

Cited by 15 publications

References 30 publications

Characterization of the Human Cysteinyl Leukotriene 2 Receptor

Characterization of the Human Cysteinyl Leukotriene 2 Receptor

Cysteinyl Leukotrienes and Their Receptors: Molecular and Functional Characteristics

P2Y₁and Cysteinyl Leukotriene Receptors Mediate Purine and Cysteinyl Leukotriene Co-Release in Primary Cultures of Rat Microglia

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Cysteinyl-Leukotriene Levels in Intracerebral Hemorrhage:An Edema-Promoting Factor?

Cited by 15 publications

References 30 publications

Characterization of the Human Cysteinyl Leukotriene 2 Receptor

Characterization of the Human Cysteinyl Leukotriene 2 Receptor

Cysteinyl Leukotrienes and Their Receptors: Molecular and Functional Characteristics

P2Y1and Cysteinyl Leukotriene Receptors Mediate Purine and Cysteinyl Leukotriene Co-Release in Primary Cultures of Rat Microglia

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P2Y₁and Cysteinyl Leukotriene Receptors Mediate Purine and Cysteinyl Leukotriene Co-Release in Primary Cultures of Rat Microglia