Prostacyclin and beraprost sodium as suppressors of activated rat polymorphonuclear leukocytes.
Beraprost sodium (beraprost) is a stable analogue of prostaglandin I2 (PGI2), 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 chemotaxis of PMNs induced by formyl-methionyl-leucyl-phenylalanine (FMLP). Like prostaglandin E2 (PGE2), beraprost elevated intracellular cAMP level and inhibited the influx of extracellular Ca2+ 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 Ca2+. 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 Ca2+ mobilization in PMNs. The above-mentioned effects of beraprost were also the case with PGI2. The potency of beraprost was comparable to PGI2 in the present study. Considering its stability, these results thus raise a possibility that beraprost might exert anti-inflammatory effect in vivo.
Kainoh
M
M
Toray Industries Inc, Basic Research Laboratories, Kanagawa, Japan.
Imai
R
R
Umetsu
T
T
Hattori
M
M
Nishio
S
S
D000818:Animals; D000838:Anions; D002118:Calcium / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D000838:Anions; D007295:Inositol Phosphates; D013481:Superoxides; C048081:beraprost; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011464:Epoprostenol; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium