Prostaglandin D2 modulates human neutrophil intracellular calcium flux and inhibits superoxide release via its ring carbonyl.
We compared the effects of prostaglandin D2 (PGD2), prostaglandin F2 alpha (PGF2) and various ketones on superoxide (OX) release by human neutrophils, which had been stimulated by N-formyl methionyl leucyl phenylalanine (FMLP). Our data suggested that the ring carbonyl of PGD2 is essential to its inhibitory effect on OX release, but the carbonyl group as a ketone, alone is not sufficient. Using the fluorescent Ca2+ probe, Fura-2AM, we found that PGD2 increased the rate of decline of FMLP stimulated intracellular free Ca2+ (Ca)i, but that PGF2 had no effect. cAMP altered FMLP stimulated (Ca)i, in a pattern similar to PGD2. Furthermore, the ring carbonyl of PGD2 is crucial to its effect on OX as well as on (Ca)i.
Simpkins
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CO
Naval Medical Research Institute, Bethesda, Maryland 20814-5055.
Mazorow
D L
DL
Alailima
S T
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Tate
E A
EA
Sweatt
W
W
Johnson
M
M
Shariff
K
K
Millar
D B
DB
D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007659:Ketones / Q000494:pharmacology; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015230:Prostaglandin D2 / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism*
D007659:Ketones; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013482:Superoxide Dismutase; D015230:Prostaglandin D2; D002118:Calcium