Activation of the prostaglandin EP4-receptor subtype is highly coupled to inhibition of N-formyl-methionyl-leucyl-phenylalanine-stimulated rat neutrophil aggregation.

The inhibitory activity of prostaglandin E2 (PGE2) on rat neutrophil aggregation has been studied using the EP4-receptor antagonist AH23848B. While AH23848B antagonized the ability of PGE2 to inhibit neutrophil aggregation stimulated by platelet-activating factor (PAF), AH23848B showed agonist activity when neutrophils were stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP). In addition, AH23848B showed weak stimulation of adenylyl cyclase activity and inhibited PGE2-stimulated [3H]cyclic AMP production by rat neutrophils, therefore AH23848B appears to be a partial agonist at EP4-receptors. These results suggest that rat neutrophils possess both inhibitory EP2- and EP4-receptors, and that FMLP-stimulated neutrophil aggregation is more highly coupled to inhibition by EP4-receptor activation than is PAF-stimulated neutrophil aggregation.