Characterization of the inhibitory prostanoid receptors on human neutrophils

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Abstract
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. Prostaglandin E2 (PGE2) and PGD2 inhibited both OZ‐induced LTB4 release (EC50 0.72 μm and 0.91 μm respectively), and FMLP‐induced O2− release (EC50 0.42 μm and 0.50 μm respectively). PGF2α, 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. 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 μm. The selective DP‐receptor agonist, BW245C, inhibited LTB4 release, (EC50 0.006 μm) 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). 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.;