The inhibitory effect of prostaglandin E2 on rat neutrophil aggregation.
Rat peritoneal neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP) produce an aggregation response that can be inhibited by prostaglandin E2 (PGE2) with an IC50 value of 2.6 x 10(-9) M. Although PGE2 can stimulate [3H]cAMP production in neutrophils (EC50 4.3 x 10(-8) M), the anti-aggregation response cannot be significantly attenuated by inhibitors of adenylate cyclase or protein kinase A, neither can it be potentiated by inhibition of phosphodiesterase activity. Despite these observations, it still remains possible that PGE2-mediated inhibition of rat neutrophil aggregation is a cAMP-dependent response mediated by highly localized changes in neutrophil cAMP. The inhibitory effect of PGE2 does not appear to depend on effects on intracellular calcium or K(ATP) channels. Similarities exist between PGE2 and the profile of activity of phosphatidylinositol 3-kinase (PI 3-kinase) inhibitors, suggesting that PI 3-kinase is a possible target for PGE2 action in rat neutrophils.
Wise
H
H
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D002449:Cell Aggregation / Q000187:drug effects*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D015232:Dinoprostone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D015221:Potassium Channels / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram; D013449:Sulfonamides; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D011760:Pyrrolidinones; D013449:Sulfonamides; C017759:9-(tetrahydro-2-furyl)-adenine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017868:Cyclic AMP-Dependent Protein Kinases; D000225:Adenine; D020889:Rolipram; D015232:Dinoprostone; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D005905:Glyburide; D000077191:Wortmannin