CHARACTERIZATION OF THE INHIBITORY PROSTANOID RECEPTORS ON HUMAN NEUTROPHILS

1 We have evaluated the effects of various prostanoid agonists on the release of leukotriene B4 (LTB4) and superoxide anions (O2-) from human neutrophils stimulated with opsonized zymosan (OZ) and formyl-methionyl-leucyl-phenylalanine (FMLP), respectively. 2 Prostaglandin E2 (PGE2) and PGD2 inhibited both OZ-induced LTB4 release (EC50 0.72 mum and 0.91 mum respectively), and FMLP-induced 02- release (EC50 0.42 mum and 0.50 mum respectively), PGF2alpha, the TP-receptor agonist, U46619, and the IP-receptor agonist, iloprost, were also active. but were all at least an order of magnitude less potent than PGE2 and PGD2. 3 The EP2/EP3-receptor agonist, misoprostol, and the selective EP2-agonist, AH13205, were both effective inhibitors of LTB4 release, being approximately equipotent with and 16-times less potent than PGE2, respectively. In contrast, the EP1/EP3-receptor agonist, sulprostone, had no inhibitory activity at concentrations of up to 10 mum. 4 The selective DP-receptor agonist, BW245C, inhibited LTB4 release, (EC50 0.006 mum) being approximately 50 times more potent than PGD2. BW245C also inhibited O2- release, and this inhibition was antagonized competitively by the DP-receptor blocking drug, AH6809 (pA2 6.6). 5 These data indicate the presence of both inhibitory EP- and DP-receptors on the human neutrophil. The rank order of potency of EP-receptor agonists suggest that the EP-receptors are of the EP2-subtype.