B. Kunievsky et E. Yavin, PRODUCTION AND METABOLISM OF PLATELET-ACTIVATING-FACTOR IN THE NORMALAND ISCHEMIC FETAL-RAT BRAIN, Journal of neurochemistry, 63(6), 1994, pp. 2144-2151
Production and metabolism of platelet-activating factor (PAF) in the f
etal rat brain under normal and under ischemic stress conditions were
examined. Endogenous PAF levels, determined by a bioassay using PAF-st
imulated platelet release of [H-3]serotonin, averaged 2.32 +/- 2.14 pg
/mg in control brains and was reduced to 1.10 +/- 1.06 pg/mg after 20
min of maternal-fetal blood flow occlusion. [H-3]PAF administered intr
acranially into the fetuses in utero was removed in a biphasic, time-d
ependent manner: a rapid component with an estimated elimination rate
constant of 0.067 min(-1) and t(1/2) of 10 min and a slower component
with an elimination rate of 0.017 min(-1) and t(1/2) of 41 min. In fet
al brains subjected to ischemia a delayed elimination of [H-3] PAF was
noticed in the slow component (t(1/2) = 59 min), indicating a possibl
e difference between the clearance of exogenous and endogenous PAF. Th
e disappearance of [H-3]PAF was accompanied by an increase in the radi
oactivity associated with lyso-PAF that reached a plateau after 2.5 mi
n, possibly indicating the degradation of the fast component. A steady
increase in the alkyl-acyl-glycerophosphorylcholine radioactivity com
menced after 5 min and continued up to 30 min. The endogenous producti
on of PAF and the rapid degradation due to maternal-fetal blood flow o
cclusion indicate an additional target for therapeutic intervention in
the pathology of intrauterine ischemia. Addition of the calcium ionop
hore A23187 stimulated in vitro formation of PAF and lyso-PAF from [H-
3]choline-labeled fetal brain phospholipids, suggesting that intracell
ular calcium may play a major stimulatory role in PAF production. Degr
adation of polyphosphoinositides by a phospholipase C may constitute a
major target for PAF generated either by decapitation or after blood
flow occlusion, as evident from the protective effect of the in vivo a
dministered BN52021 PAF antagonist.