The metabolism of 1-acyl-PAF in rabbit platelets and its possible interaction with PAF |
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Authors: | Lhousseine Touqui Clystenes Soares Silva Bernardo Boris Vargaffig |
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Affiliation: | 1. Unite de Pharmacologie Cellulaire, Unite Associee INSERM/Pasteur U.285, Institut Pasteur, 28 rue Dr. Roux, 75015, Paris, France
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Abstract: | The metabolism of 1-acyl-2-acetyl-sn-glycero-3-phosphocholine (1-acyl-PAF), a naturally occurring analogue of platelet activating factor (PAF), was investigated
in rabbit platelets. Our studies showed that 1-acyl-3H]PAF (1-palmitoyl-2-acetyl-sn-glycero-3-phosphoN-methyl-3H]-choline) was converted by platelets into phosphatidyl-3H]choline (3H]PC) in a time-dependent fashion. The formation of 3H]PC occurred at a rate similar to that observed when lyso-3H]PC (palmitoyl-sn-glycero-3-phosphoN-methyl-3H]choline) was used as substrate. In addition, a time-dependent increase in the level of water-soluble radioactivity was observed
during the incubation of platelets with either 1-acyl-3H]PAF or lyso-3H]PC. This increase was parallel to the formation of 3H]PC and was not observed in the presence of 14C]PAF (1-octadecyl-2-acetyl-sn-glycerol-3-phosphoN methyl-14C]choline). Analysis by thin-layer chromatography showed that the soluble radioactivity was mainly associated with glycerophosphocholine
(GPC). On the other hand, the preincubation of platelets with phenylmethylsulfonyl fluoride, an inhibitor of the acetylhydrolase,
reduced the hydrolysis of 1-acyl-3H]PAF to 3H]GPC with a concomitant accumulation of radioactivity in 1-acyl-PAF. These findings suggest that 1-acyl-PAF is converted
into PC through deacetylation-reacylation with lysoPC as an obligatory intermediate. The findings also indicate that the lysoPC
resulting from 1-acyl-PAF is either reacylated to phosphatidylcholine (PC) or hydrolyzed to GPC by lysophospholipase. Finally,
we showed that the stimulation of platelets with PAF led to a time- and concentration-dependent increase in the conversion
of 1-acyl-3H]PAF to 3H]PC. The stimulatory effect of PAF was not observed when platelets were lysed before incubation, suggesting that PAF enhances
the metabolism of 1-acyl-PAF, probably by accelerating its translocation through the plasma membrane. |
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