Nishio Shintaro

Prostacyclin and beraprost sodium as suppressors of activated rat polymorphonuclear leukocytes

Abstract Beraprost sodium (beraprost) is a stable analogue of prostaglandin I 2 (PGI 2 ), which can be administrated orally. In the present study, the effect of beraprost on the activation process of polymorphonuclear leukocytes (PMNs) was examined in vitro . Beraprost effectively inhibited chemo-taxis of PMNs induced by formyl-methionyl-leucyl-phenylalanine (FMLP). Like prostaglandin E 2 (PGE 2 ), beraprost elevated intracellular cAMP level and inhibited the influx of extracellular Ca 2+ in PMNs. The concentration-response curves showed that the inhibitory effect of beraprost on chemotaxis was correlated with the increment of intracellular cAMP level of the PMNs and inhibition of influx of extracellular Ca 2+ . Beraprost also inhibited inositol phospholipid metabolic turnover and Superoxide anion production of PMNs induced by FMLP at relatively high concentration. These results suggest that the inhibitory effect of beraprost on the PMN function especially chemotaxis is mediated through the elevation of the intracellular cAMP level, which interferes with the signal transduction process probably through the inhibition of Ca 2+ mobilization in PMNs. The above-mentioned effects of beraprost were also the case with PGI 2 . The potency of beraprost was comparable to PGI 2 in the present study. Considering its stability, these results thus raise a possibility that beraprost might exert anti-inflammatory effect in vivo .