Effect of CGS 25019C and other LTB4 antagonists in the mouse ear edema and rat neutropenia models

Raychaudhuri, A.; Kotyuk, Bernard; Pellas, Theodore C.; Pastor, Gary; Fryer, L R; Morrissey, Margaret C.; Main, Alan J.

doi:10.1007/bf01778302

Cited by 14 publications

(9 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In FLIPR experiments, 5-oxo-ETE induced a concentration-dependent increase of intracellular calcium in a R527/ HEKG␣ 16 stable cell line; this effect was not inhibited by the cysLT1R and LTB4 receptor antagonists CGS25019C (Bray et al, 1991) or CGP45715A (Raychaudhuri et al, 1995), respectively. In addition, leukotrienes LTB 4 , LTC 4 , and LTD 4 did not induce calcium mobilization in the R527 stable cell line, suggesting that the effects of 5-oxo-ETE are independent of the LTB 4 or cysLT receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Leukotrienes LTB 4 , LTC 4 , LTD 4 , and LTE 4 were tested for their activity against the stable R527/HEKG␣ 16 cell line but no calcium mobilization activity was observed. The cysLT1R antagonist CGP45715A (Bray et al, 1991) and the LTB 4 receptor antagonist CGS25019C (Raychaudhuri et al, 1995) were analyzed for their effects on 5-oxo-ETE induced increases in intracellular calcium. No inhibition of the 5-oxo-ETE signal was observed for antagonist concentrations of up to 10 M (data not shown).…”

Section: Generation Of Stable Cell Lines Expressing R527mentioning

confidence: 99%

See 1 more Smart Citation

Expression and Characterization of a 5-oxo-6E,8Z,11Z,14Z-Eicosatetraenoic Acid Receptor Highly Expressed on Human Eosinophils and Neutrophils

et al. 2003

View full text Add to dashboard Cite

Using a bioinformatics approach, we have isolated a novel Gprotein-coupled receptor (GPCR), R527, and have demonstrated that this receptor shows no significant homology to previously deorphanized GPCRs. Quantitative reverse transcription-polymerase chain reaction analysis of the expression of GPCR R527 indicated a very high level of mRNA expression in eosinophils, with high expression also detected in neutrophils and lung macrophages. Stable cell lines were generated expressing this receptor together with the G-protein ␣-subunit G␣ 16 . These cells were used to screen an agonist collection in a calcium mobilization assay and 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) was identified as a putative ligand. 5(S)-Hydroxyperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid was also shown to activate the receptor, whereas the leukotrienes LTB 4 , LTC 4 , LTD 4 , and LTE 4 failed to elicit a response. In cAMP assays, pertussis toxin reversed the inhibitory effects of 5-oxo-ETE on cAMP production, indicating that the receptor is G␣ i -coupled. The GPCR R527 shows pharmacological properties similar to those of the previously described 5-oxo-ETE receptor expressed on eosinophils, neutrophils, and monocytes. These cell types show chemotactic responses to 5-oxo-ETE, and this eicosanoid has been proposed to play a key role in the inflammatory response. The molecular identification of a receptor binding 5-oxo-ETE will expand our understanding of the physiological role of this mediator and may provide new therapeutic opportunities.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Generation Of Stable Cell Lines Expressing R527mentioning

confidence: 99%

Expression and Characterization of a 5-oxo-6E,8Z,11Z,14Z-Eicosatetraenoic Acid Receptor Highly Expressed on Human Eosinophils and Neutrophils

et al. 2003

View full text Add to dashboard Cite

show abstract

“…36,37) Further confirming this, blockade of COX-2, iNOS, and 5-LO was shown to be efficacious in these in vivo models as well as in RAW264.7 cell models. [38][39][40][41][42] In summary, we found that SKLJI intravenous injection potently inhibits croton oil-and arachidonic acid-induced mouse ear edema. It reduced acetic acidinduced writhing numbers and carrageenan-induced hindpaw hyperalgesia at low doses.…”

mentioning

confidence: 83%

Anti-Inflammatory and Analgesic Activities of SKLJI, a Highly Purified and Injectable Herbal Extract of Lonicera japonica

Ryu

Rhee

Kim

et al. 2010

Bioscience, Biotechnology, and Biochemistry

View full text Add to dashboard Cite

“…Compound 56 also blocked edema formation and neutrophil influx following AA application to the mouse ear with ED 50 values of 1.4 and 1.8 mg/kg po. 224 In comparison, 50 (3 mg/kg po) inhibited edema and neutrophil influx by 30% and 40%, respectively. Compound 56 also blocked collagen-induced arthritis in the rat in a dose-dependent manner when administered orally at doses of 1, 3, and 10 mg/kg.…”

Section: Leukotriene B 4 Antagonists That Have Progressed To Clinicalmentioning

confidence: 97%

Modulators of Leukotriene Biosynthesis and Receptor Activation

1996

View full text Add to dashboard Cite

IntroductionThe history of leukotriene (LT) research has been documented in numerous articles and reviews since the discovery of the LT biosynthetic pathway 1 and the delineation of the various chemical structures involved in the pathway and their total synthesis. 2 Three previous Perspective articles have provided periodic updates, the first in 1981, 3 the second 1 decade later covering LT receptor antagonists, 4 and the third in 1992 covering LT biosynthesis inhibitors. 5 With this background, the task of this Perspective is to update the status of LT intervention research by providing an overview of the leading enzyme inhibitors and receptor antagonists as well as the status of clinical trials with these agents and how the latter are influencing the development of new therapeutic modalities for the treatment of inflammation and allergy.The clinical proof-of-concept for LT intervention has taken longer than expected considering that the biosynthesis and chemical composition of LTs were delineated by 1979. It is now clear that LT intervention therapy represents a promising new modality for the treatment of asthma. Several compounds including the 5-lipoxygenase (5-LO) inhibitor zileuton (1) and the cysteinyl LT antagonist zafirlukast (2) have completed pivotal clinical trials, while several other LT modulators are progressing to this stage. Within a few years the therapeutic potential of these new agents in asthma and other inflammatory and allergic disorders will be evident. Leukotriene Intervention StrategiesLeukotriene Biosynthesis. Leukotrienes are biosynthesized via the 5-LO (arachidonate:oxygen 5-oxidoreductase, EC 1.13.11.34) pathway of arachidonic acid (AA) metabolism ( Figure 1). The 5-LO product LTA 4 is a pivotal reactive epoxide intermediate in an important branch in the biosynthetic pathway that is further metabolized by either (i) stereoselective hydration by LTA 4 hydrolase to LTB 4 or (ii) glutathione addition by LTC 4 synthase to LTC 4 . Successive amino acid cleavage steps convert LTC 4 to LTD 4 and then to LTE 4 . The cysteinyl LTs (LTC 4 , LTD 4 , LTE 4 ) are the constituents of the biological substance previously known as slowreacting substance of anaphlyaxis (SRS-A). 6 LTB 4 is a very potent neutrophil chemotactic agent, inducing neutrophil adherence to endothelial cells, degranulation, and modulation of cytokine production. The biosynthesis, release, and recovery of LTs from specific cells involved in inflammatory disorders together with the observed ability of these products to mimic aspects of disease support their involvement as mediators of inflammatory and allergic disorders. 7,8 Despite such circumstantial evidence, confirmation of the pathophysiological role of these mediators requires selective blockade of their actions.At the outset of research efforts in the LT area, it was not entirely clear which LTs or subsequent metabolites were the predominant mediators of a particular human disorder. LTs are short-lived, being rapidly converted to inactive metabolites, and prolonged expressi...

show abstract

Effect of CGS 25019C and other LTB4 antagonists in the mouse ear edema and rat neutropenia models

Cited by 14 publications

References 5 publications

Expression and Characterization of a 5-oxo-6E,8Z,11Z,14Z-Eicosatetraenoic Acid Receptor Highly Expressed on Human Eosinophils and Neutrophils

Expression and Characterization of a 5-oxo-6E,8Z,11Z,14Z-Eicosatetraenoic Acid Receptor Highly Expressed on Human Eosinophils and Neutrophils

Anti-Inflammatory and Analgesic Activities of SKLJI, a Highly Purified and Injectable Herbal Extract of Lonicera japonica

Modulators of Leukotriene Biosynthesis and Receptor Activation

Contact Info

Product

Resources

About