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.
Wise
H
H
Department of Pharmacology, The Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories. helenwise@cuhk.edu.hk
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002449:Cell Aggregation / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D020889:Rolipram
D001713:Biphenyl Compounds; D010726:Phosphodiesterase Inhibitors; D010972:Platelet Activating Factor; D011760:Pyrrolidinones; D018078:Receptors, Prostaglandin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; C046926:AH 23848; D011464:Epoprostenol; D000242:Cyclic AMP; D020889:Rolipram; D015232:Dinoprostone; C043867:cicaprost