The inhibitory effects of non-prostanoid prostacyclin mimetics on rat neutrophil function.
The effects of three non-prostanoid prostacyclin mimetics on rat peritoneal neutrophil activity have been investigated and compared with the effects of the prostacyclin analogues cicaprost and iloprost. Cicaprost, iloprost, BMY 22389 (octimibate), BMY 42393 and BMY 45778 inhibited N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophil aggregation with IC50 values of 2.1, 4.5, 286, 462 and 20 nM, respectively. Cicaprost and iloprost produced clear concentration-related increases in [3H]cyclic AMP accumulation; EC50 values were 20 and 44 nM, respectively. In contrast, the three BMY compounds showed low efficacy as activators of adenylyl cyclase. The inhibitory effect of prostacyclin mimetics does not appear to depend on effects on intracellular calcium concentration, or on KATP channels. Extensive studies using cyclic AMP mimetics and antagonists suggest that the anti-aggregatory activity of the non-prostanoid prostacyclin mimetics on rat neutrophils may involve highly localized increases in cyclic AMP.
Wise
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Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong.
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D016285:Iloprost / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology*; D010642:Phenoxyacetates / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000819:agonists
D000085:Acetates; D007093:Imidazoles; D010080:Oxazoles; D010642:Phenoxyacetates; D010726:Phosphodiesterase Inhibitors; D011465:Prostaglandins, Synthetic; D011982:Receptors, Prostaglandin; C080116:BMY 42393; C084677:BMY 45778; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011464:Epoprostenol; D000242:Cyclic AMP; D016285:Iloprost; C043867:cicaprost; C054659:octimibate; D005905:Glyburide; D002118:Calcium