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Prostaglandin modulation of N -formylmethionylleucylphenylalanine-induced transmembrane potential changes in rat neutrophils

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, ISSN: 0167-4889, Vol: 804, Issue: 3, Page: 265-274
1984
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Article Description

Prostaglandins of the E-series (PGEs) and PGI 2 will inhibit formylmethionylleucylphenylalanine- (f-Met-Leu-Phe) induced lysosomal enzyme release and superoxide-anion (O − 2 ) production by neutrophils. The inhibitory effects of PGEs and PGI 2 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 PGI 2 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-PGE 1 (15-methyl-PGE 1 ), a stable analogue of PGE 1 and PGI 2 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 O − 2 production and degranulation. In contrast, 15-methyl-PGE 1 and PGI 2, did not inhibit phorbol-myristate-acetate-induced transmembrane potential changes and O − 2 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.

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