The inhibitory effect of prostaglandin E(2) on rat neutrophil aggregation

Rat peritoneal neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP) produce an aggregation response that can be inhibited by prostaglandin E(2) (PGE(2)) with an IC50 value of 2.6 x 10(-9) M. Although PGE(2) can stimulate [H-3]cAMP production in neutrophils (EC(50) 4.3 x 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, Despite these observations, it still remains possible that PGE(2)-mediated inhibition of rat neutrophil aggregation is a cAMP-dependent response mediated by highly localized changes in neutrophil cAMP. The inhibitory effect of PGE(2) does not appear to depend on effects on intracellular calcium or K-ATP channels, Similarities exist between PGE(2) and the profile of activity of phosphatidylinositol 3-kinase (PI 3-kinase) inhibitors, suggesting that PI 3-kinase is a possible target for PGE(2) action in rat neutrophils.