Characterization of Thromboxane Receptors in Human Platelets

Jones, R. L.; Wilson, Nick; Armstrong, Roma A.

doi:10.1007/978-1-4615-9442-0_6

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…Elegant studies performed over the last 15 years (for example see Armstrong et al , 1983; Jones et al , 1985; Dong et al , 1986; and reviews by Kennedy et al , 1982; Coleman et al , 1984; 1994b) have provided pharmacological evidence for five main classes of receptor for the naturally occurring prostanoid agonists. These receptors have been given the prefix DP‐, EP‐, FP‐, IP‐ and TP‐ and belong to the G‐protein‐coupled receptor superfamily with seven transmembrane‐spanning domains.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the prostanoid receptor(s) on human blood monocytes at which prostaglandin E₂ inhibits lipopolysaccharide‐induced tumour necrosis factor‐α generation

Meja

Barnes

Giembycz

1997

British J Pharmacology

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1 The prostanoid receptor(s) that mediates inhibition of bacterial lipopolysaccharide (LPS)-induced tumour necrosis factor-a (TNFa) generation from human peripheral blood monocytes was classi®ed by use of naturally occurring and synthetic prostanoid agonists and antagonists. 2 In human monocytes that were adherent to plastic, neither prostaglandin D 2 (PGD 2 ), prostaglandin E 2 (PGE 2 ), prostaglandin F 2a (PGF 2a ) nor the stable prostacyclin and thromboxane mimetics, cicaprost and U-46619, respectively, promoted the elaboration of TNFa-like immunoreactivity, as assessed with a speci®c ELISA, indicating the absence of excitatory prostanoid receptors on these cells. 3 Exposure of human monocytes to LPS (3 ng ml 71 , * EC 84 ) resulted in a time-dependent elaboration of TNFa which was suppressed in cells pretreated with prostaglandin E 1 (PGE 1 ), PGE 2 and cicaprost. This e ect was concentration-dependent with mean pIC 50 values of 7.14, 7.34 and 8.00 for PGE 1 , PGE 2 and cicaprost, respectively. PGD 2 , PGF 2a and U-46619 failed to inhibit the generation of TNFa at concentrations up to 10 mM. 4 With respect to PGE 2 , the EP-receptor agonists, 16,16-dimethyl PGE 2 (non-selective), misoprostol (EP 2 /EP 3 -selective), 11-deoxy PGE 1 (EP 2 -selective) and butaprost (EP 2 -selective) were essentially full agonists as inhibitors of LPS-induced TNFa generation with mean pIC 50 values of 6.21, 6.02, 5.67 and 5.59, respectively. In contrast to the results obtained with butaprost and 11-deoxy PGE 1 , another EP 2 -selective agonist, AH 13205, inhibited TNFa generation by only 21% at the highest concentration (10 mM) examined. EP-receptor agonists which have selectivity for the EP 1 -(17-phenyl-o-trinor PGE 2 ) and EP 3 -receptor (MB 28,767, sulprostone) were inactive or only weakly active as inhibitors of TNFa generation. 5 Pretreatment of human monocytes with the TP/EP 4 -receptor antagonist, AH 23848B, at 10, 30 and 100 mM suppressed LPS-induced TNFa generation by 10%, 28% and 77%, respectively, but failed to shift signi®cantly the location of the PGE 2 concentration-response curves. 6 Given that AH 13205 was a poor inhibitor of TNFa generation, studies were performed to determine if it was a partial agonist and whether it could antagonize the inhibitory e ect of PGE 2 . Pretreatment of human monocytes with 10 and 30 mM AH 13205 inhibited the generation of TNFa by 31% and 53%, respectively, but failed to shift signi®cantly the location of the PGE 2 concentration-response curves at either concentration examined. 7 Since PGD 2 and 17-phenyl-o-trinor PGE 2 (EP 1 -agonist) did not suppress TNFa generation, the EP 1 / EP 2 /DP-receptor antagonist, AH 6809, was employed to assess if EP 2 -receptors mediated the inhibitory e ect of PGE 2 . Pretreatment of human monocytes with 10 mM AH 6809 did not a ect LPS-induced TNFa generation but produced a parallel 3.5 fold rightwards shift of the PGE 2 concentration-response curve. 8 Collectively, these data suggest that human peripheral blood monocytes express at least two distin...

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Section: Introductionmentioning

confidence: 99%

Characterization of the prostanoid receptor(s) on human blood monocytes at which prostaglandin E₂ inhibits lipopolysaccharide‐induced tumour necrosis factor‐α generation

Meja

Barnes

Giembycz

1997

British J Pharmacology

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“…This might indicate platelet activation not immediately after exposure to altitude rather at later time point. TXA2 is responsible for multiple biological processes through the cell surface TXA2 receptor, or T-prostanoid (TP) receptor [ 41 , 42 ]. Activation of gene transcript TBXA2R log2 fold change = 1.07 is also observed at HAD7 in Kyrgyz.…”

Section: Discussionmentioning

confidence: 99%

Temporal transcriptome analysis suggest modulation of multiple pathways and gene network involved in cell-cell interaction during early phase of high altitude exposure

et al. 2020

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High altitude (HA) conditions induce several physiological and molecular changes, prevalent in individuals who are unexposed to this environment. Individuals exposed towards HA hypoxia yields physiological and molecular orchestration to maintain adequate tissue oxygen delivery and supply at altitude. This study aimed to understand the temporal changes at altitude of 4,111m. Physiological parameters and transcriptome study was conducted at high altitude day 3, 7, 14 and 21. We observed changes in differentially expressed gene (DEG) at high altitude time points along with altered BP, HR, SpO 2 , mPAP. Physiological changes and unsupervised learning of DEG's discloses high altitude day 3 as distinct time point. Gene enrichment analysis of ontologies and pathways indicate cellular dynamics and immune response involvement in early day exposure and later stable response. Major clustering of genes involved in cellular dynamics deployed into broad categories: cell-cell interaction, blood signaling, coagulation system, and cellular process. Our data reveals genes and pathways perturbed for conditions like vascular remodeling, cellular homeostasis. In this study we found the nodal point of the gene interactive network and candidate gene controlling many cellular interactive pathways VIM, CORO1A, CD37, STMN1, RHOC, PDE7B, NELL1, NRP1 and TAGLN and the most significant among them i.e. VIM gene was identified as top hub gene. This study suggests a unique physiological and molecular perturbation likely to play a critical role in high altitude associated pathophysiological condition during early exposure compared to later time points.

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“…The thromboxane A2 receptor (TBXA2R) is a G protein-coupled receptor (GPCR) that mediates platelet activation and aggregation in response to thromboxane A2 (TXA2), a short half-life (~30 s) prostaglandin derivative (Jones et al, 1985). TXA2 also controls other functions, such as vasoconstriction, inflammation, and angiogenesis (Nakahata, 2008).…”

Section: Introductionmentioning

confidence: 99%

The G protein-coupled receptor TBXA2R activates ERMs to control cell motility and invasion of triple-negative breast cancer cells.

Leguay

Naffati

et al. 2023

Preprint

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Metastasis, the process by which cancer cells colonize distant organs, relies on the ability of these cells to migrate and invade the surrounding tissues. The ezrin, radixin, and moesin family (ERM) of proteins are critical regulators of cell morphology transformations required for cancer cell movement and invasion. Yet, how ERMs are activated during metastasis remains poorly understood. Here, we identified the thromboxane A2 receptor (TBXA2R), a G protein-coupled receptor, as a critical activator of ERMs that promotes motility, invasion, and metastasis of triple-negative breast cancer (TNBC) cells. We found that ERM activation downstream of TBXA2R signaling depends on the Gαq/11 and Gα12/13 subfamilies, the small GTPase RhoA, and its Ser/Thr kinase effector SLK. We also showed that TBXA2R signaling increases TNBC cell motility and invasion in vitro and metastasis in vivo, depending on ERMs. These findings unveil a novel mechanism by which a member of the largest class of receptors activates key metastatic determinants to promote TNBC metastasis, which could have important implications for developing novel therapeutic strategies.

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Characterization of Thromboxane Receptors in Human Platelets

Cited by 9 publications

References 31 publications

Characterization of the prostanoid receptor(s) on human blood monocytes at which prostaglandin E₂ inhibits lipopolysaccharide‐induced tumour necrosis factor‐α generation

Characterization of the prostanoid receptor(s) on human blood monocytes at which prostaglandin E₂ inhibits lipopolysaccharide‐induced tumour necrosis factor‐α generation

Temporal transcriptome analysis suggest modulation of multiple pathways and gene network involved in cell-cell interaction during early phase of high altitude exposure

The G protein-coupled receptor TBXA2R activates ERMs to control cell motility and invasion of triple-negative breast cancer cells.

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Characterization of Thromboxane Receptors in Human Platelets

Cited by 9 publications

References 31 publications

Characterization of the prostanoid receptor(s) on human blood monocytes at which prostaglandin E2 inhibits lipopolysaccharide‐induced tumour necrosis factor‐α generation

Characterization of the prostanoid receptor(s) on human blood monocytes at which prostaglandin E2 inhibits lipopolysaccharide‐induced tumour necrosis factor‐α generation

Temporal transcriptome analysis suggest modulation of multiple pathways and gene network involved in cell-cell interaction during early phase of high altitude exposure

The G protein-coupled receptor TBXA2R activates ERMs to control cell motility and invasion of triple-negative breast cancer cells.

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Characterization of the prostanoid receptor(s) on human blood monocytes at which prostaglandin E₂ inhibits lipopolysaccharide‐induced tumour necrosis factor‐α generation

Characterization of the prostanoid receptor(s) on human blood monocytes at which prostaglandin E₂ inhibits lipopolysaccharide‐induced tumour necrosis factor‐α generation