Prostaglandin modulation of N-formylmethionylleucylphenylalanine-induced transmembrane potential changes in rat neutrophils.
Prostaglandins of the E-series (PGEs) and PGI2 will inhibit formylmethionylleucylphenylalanine-(f-Met-Leu-Phe) induced lysosomal enzyme release and superoxide-anion (O2-) production by neutrophils. The inhibitory effects of PGEs and PGI2 on neutrophil functional responses have been correlated with their ability to increase intracellular cAMP. In this study we have examined the effects of PGEs and PGI2 on f-Met-Leu-Phe- and phorbol-myristate-acetate-induced rat neutrophil membrane potential changes using an optical probe of membrane potential 3,3-dipropylthiodicarbocyanine iodide. 15-(S)-15-methyl-PGE1 (15-methyl-PGE1), a stable analogue of PGE1 and PGI2 inhibited f-Met-Leu-Phe-induced transmembrane potential changes in a dose-dependent manner. This inhibition was correlated with the ability of these agents to increase intracellular cAMP levels and inhibit O2- production and degranulation. In contrast, 15-methyl-PGE1 and PGI2, did not inhibit phorbol-myristate-acetate-induced transmembrane potential changes and O2- production. These results suggest independent mechanisms of activation of neutrophils by phorbol myristate acetate and f-Met-Leu-Phe, and they also suggest that the inhibitory effects of prostaglandins and cAMP on f-Met-Leu-Phe-stimulated cells is at a step or steps prior to activation of those processes involved in effecting changes in transmembrane potential, which are common to both stimuli.
D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000502:physiology*; D011458:Prostaglandins E / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; C025170:15(S)-15-methylprostaglandin E1; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003994:Bucladesine; D011464:Epoprostenol; D000242:Cyclic AMP; D000527:Alprostadil; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate