Characterization of prostanoid receptors on rat neutrophils

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Abstract
1 The effects of various prostanoid agonists have been compared on the increase in intracellular free calcium ([Ca2+]i) and the aggregation reaction of rat peritoneal neutrophils induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). 2 Prostaglandin E2 (PGE2) and the specific IP-receptor agonist, cicaprost, both inhibited the FMLP-induced increase in [Ca2+]i (IC50 33 nm and 18 nm respectively) and the FMLP-induced aggregation reaction (IC50 5.6 nm and 7.9 nm respectively). PGD2, PGF2α, and the TP-receptor agonist, U 46619, were inactive at the highest concentration tested (1 μm). 3 The EP1receptor agonist, 17-phenyl-ω-trinor PGE2, and the EP3-receptor agonists, GR 63799X and sulprostone, had no inhibitory effect on FMLP-stimulated rat neutrophils. 4 PGE1 (EP/IP-receptor agonist) and iloprost (IP-receptor agonist) inhibited the FMLP-induced increase in [Ca2+]i with IC50 values of 34 nm and 38 nm respectively. The EP2-receptor agonists, butaprost and misoprostol (1 μm), inhibited both FMLP-stimulated [Ca2+]i and aggregation. However another EP2-receptor agonist, AH 13205, was inactive in both assays. 5 Prostanoid receptors present on rat neutrophils were further characterized by measuring [3H]-adenosine 3′:5′-cyclic monophosphate ([3H]-cyclic AMP) accumulation. Only those agonists capable of stimulating [3H]-cyclic AMP accumulation were able to inhibit both FMLP-stimulated [Ca2+]i and aggregation. 6 These results indicate that rat neutrophils possess inhibitory IP and EP-receptors; the relative potencies of PGE2, misoprostol and butaprost are those expected for the EP2-receptor subtype. No evidence for DP, FP, TP or EP1 and EP3-receptors was obtained.