Effects of prostacyclin analogs on cyclic adenosine monophosphate and superoxide formation in human polymorphonuclear leukocytes stimulated by formyl-methionyl-leucyl-phenylalanine.
The modulation of cyclic AMP levels and superoxide release in isolated FMLP-stimulated human PMN by two oxacyclic analogs and one carbacyclic analog of PGI2 and by PGE1 is investigated over a wide range of concentrations of the test compounds. The prostacyclin analogs only marginally increase the cyclic AMP levels in unstimulated PMN but like PGE1 potentiate the FMLP-induced rise in cyclic AMP. The concentration dependency is bell-shaped with a maximum effect at about 10 microM of the prostanoids. In contrast, all prostanoids dose-dependently inhibit FMLP-induced superoxide release almost to completion. The relative inhibitory potency of the prostacyclin analogs corresponds to their prostacyclin-like action in other systems. It is therefore suggested that PMN contain prostacyclin receptors, which, however, have weaker affinities than those in platelets. The lack of correlation between inhibition of superoxide formation and modulation of the cyclic AMP system rules out the possibility that cyclic AMP can simply be considered the second messenger of prostacyclins in PMN. The potential biological relevance of the effects of prostacyclin-like compounds on PMN functions is discussed.
Stahlberg
H J
HJ
Grünenthal GmbH, Center of Research, Aachen.
Loschen
G
G
Flohé
L
L
D000242:Cyclic AMP / Q000097:blood*; D011464:Epoprostenol / Q000494:pharmacology / Q000031:analogs & derivatives; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D013481:Superoxides / Q000097:blood*
D011465:Prostaglandins, Synthetic; C057200:CG 4303; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C050548:naxaprostene; C039188:taprostene; D011464:Epoprostenol; D000242:Cyclic AMP