Characterization of the PGE receptor subtype mediating inhibition of superoxide production in human neutrophils

  title={Characterization of the PGE receptor subtype mediating inhibition of superoxide production in human neutrophils},
  author={Elisabeth Talpain and Roma A. Armstrong and Robert A. Coleman and Christopher J. Vardey},
  journal={British Journal of Pharmacology},
1 The aims of this study were to characterize the EP receptor subtype mediating the inhibition of superoxide anion generation by formyl methionyl leucine phenylalanine (FMLP)‐stimulated human neutrophils, and to test the hypothesis that adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) is the second messenger mediating the inhibition of the neutrophil by prostaglandin (PG)E2. 

Prostaglandin E2 inhibits neutrophil extracellular trap formation through production of cyclic AMP

Upon stimulation, neutrophils release their nuclear contents called neutrophil extracellular traps (NETs), which contain unfolded chromatin and lysosomal enzymes. NETs have been demonstrated to play

Investigation of the inhibitory effects of PGE2 and selective EP agonists on chemotaxis of human neutrophils

  • R. Armstrong
  • Biology, Medicine
    British journal of pharmacology
  • 1995
The hypothesis that cyclic AMP is the second messenger involved in prostaglandin E2‐stimulated human neutrophils is tested, and the inhibitory effects of selective EP agonists and type IV phosphodiesterase (PDE) inhibitors, rolipram and Ro20‐1724 have been examined.

The inhibitory effect of prostaglandin E2 on rat neutrophil aggregation

  • H. Wise
  • Biology
    Journal of leukocyte biology
  • 1996
Although PGE2 can stimulate [3H]cAMP production in neutrophils (EC50 4.3 10‐8 M), the anti‐aggregation response cannot be significantly attenuated by inhibitors of adenylate cyclase or protein kinase A, neither can it be potentiated by inhibition of phosphodiesterase activity.

Prostaglandin E2 inhibits the phospholipase D pathway stimulated by formyl-methionyl-leucyl-phenylalanine in human neutrophils. Involvement of EP2 receptors and phosphatidylinositol 3-kinase gamma.

Examination of the effects of PGE(2) and prostaglandin E (EP) receptor-selective agonists/antagonists on several steps of the formyl-methionyl-leucyl-phenylalanine (fMLP)-induced phospholipase D (PLD) activation pathway in human neutrophils provides strong evidence that the inhibitory effects of FMLP-induced PLD activation pathway were mediated via EP( 2) receptors.

Investigation of the role of nitric oxide and cyclic GMP in both the activation and inhibition of human neutrophils

The finding that the guanylyl cyclase inhibitor LY 83583 completely inhibited chemotaxis and suppressed the maximal response suggests NO is a mediator of fMLP‐induced SAG, suggesting the paradox that NO both activates and inhibits human neutrophils is resolved.

Differential sensitivity of macrophages to bradykinin

The findings indicate that the stage of differentiation/maturation and activation of macrophages may be important for the ability of bradykinin to stimulate these cells to inflammatory responses in vivo.

Histamine up-regulates phosphodiesterase 4 activity and reduces prostaglandin E2-inhibitory effects in human neutrophils

Histamine up-regulates PDE4 activity and produces heterologous desensitisation of human neutrophils and reduced the inhibition by prostaglandin E2 of zymosan-induced superoxide generation.

Role of Cyclooxygenase in the Chorionic Gonadotropin Regulation of Human Neutrophil Activity

Data indicate that realization of the suppressive effects of chorionic gonadotropin in the neutrophils is partially linked with activation of cyclooxygenase (both the constitutive and inducible forms of the enzyme).

Activation of neutrophil-like HL-60 cells by prostaglandin E2.

  • H. WiseZ. Xie
  • Biology, Medicine
    Prostaglandins, leukotrienes, and essential fatty acids
  • 1996



Stimulus-dependent inhibition of superoxide generation by prostaglandins.

Inhibition of the n-formylmethionyl-leucyl-phenylalanine induced respiratory burst in human neutrophils by adrenergic agonists and prostaglandins of the E series.

  • K. WongK. Freund
  • Biology, Medicine
    Canadian journal of physiology and pharmacology
  • 1981
Exogenous prostaglandins E1 and E2 and L-isoproterenol potently inhibited the production of superoxide anions by human neutrophils activated in vitro by n-formylmethionyl-leucyl-phenylalanine (FMLP).

PGD2 and its mimetic ZK 110.841 are potent inhibitors of receptor-mediated activation of human neutrophils.

An effective inhibition of receptor-mediated (FMLP, PAF) PMN activation by PGD2 and its mimetic ZK 110.841 is demonstrated, suggesting either an inhibitory PGD 2 receptor on human PMN or action of PGD1 at the PGE receptor.

Characterization of the inhibitory prostanoid receptors on human neutrophils

The rank order of potency of EP‐receptor agonists suggest that theEP‐receptors are of the EP2‐subtype; these data indicate the presence of both inhibitory EP‐ and DP‐ receptors on the human neutrophil.

Characterization of receptors involved in the direct and indirect actions of prostaglandins E and I on the guinea‐pig ileum

It is felt that the preparation must be used with caution to ascertain the EP1 agonist or antagonist potencies of novel compounds, and that EP2‐receptors may be involved in the PGE action, in view of the marked effect of morphine on the contractile actions of misoprostol,11‐deoxy PGE2‐1‐alcohol, 11‐de oxygen PGE1 and butaprost.

Occupancy of adenosine receptors raises cyclic AMP alone and in synergy with occupancy of chemoattractant receptors and inhibits membrane depolarization.

Adenosine occupies an A2 receptor on neutrophils to raise intracellular cAMP in synergy with occupancy of the FMLP receptor, and indicates that cAMP is not the second messenger for inhibition of O2- generation by adenosine and its analogues.

Mechanisms of lysosomal enzyme release from human leukocytes. II. Effects of cAMP and cGMP, autonomic agonists, and agents which affect microtubule function.

The data suggest that granule movement and acid hydrolase release from leukocyte lysosomes requires intact microtubules and may be modulated by adrenergic and cholinergic agents which appear to provoke changes in concentrations of cyclic nucleotides.