Production and effects of platelet-activating factor in the rat brain.
The synthesis of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in rat brain was evaluated. Extracted PAF was characterized using standard HPLC and TLC techniques, and by correlation of its bioactivity with the acetylation state of the 2-position of the molecule. PAF was quantified by bioassay, its ability to cause [3H]serotonin release from washed rabbit platelets. The low basal level of PAF (0.25 +/- 0.15 pmol/g wet wt., mean +/- S.E.) in the brain of the intact rat was greatly increased by intraperitoneal injection of the chemoconvulsant drugs picrotoxin or bicuculline, to levels of 10.68 +/- 2.18 and 4.97 +/- 0.75 pmol/g wet wt., respectively. Electroconvulsion also increased brain PAF, to 1.76 +/- 0.30 pmol/g wet wt. Equivalent experiments using bicuculline in the isolated perfused rat brain yielded qualitatively similar results, indicating that the production of PAF in the brain is independent of systemic metabolism. When a 32P-labeled nerve-ending (synaptosome) preparation from rat brain was challenged with synthetic PAF (denoted AGEPC) at 0.1 nM concentration, responses were observed consistent with accelerated turnover of polyphosphoinositides. AGEPC also caused an increase in the Na+-Ca2+ exchange of synaptic membrane vesicles. Furthermore, AGEPC infused into the vasculature of the isolated perfused rat brain caused changes consistent with an increase in blood-brain barrier permeability, although AGEPC did not itself significantly penetrate the blood-brain barrier. It is concluded from these studies that PAF is synthesized within the rat brain in response to convulsant stimuli and that one of its effects is to accelerate synaptic polyphosphoinositide turnover. In addition, circulating PAF can influence blood-brain barrier permeability without itself penetrating the blood-brain barrier.
Kumar
R
R
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
Harvey
S A
SA
Kester
M
M
Hanahan
D J
DJ
Olson
M S
MS
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010710:Phosphates / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D010710:Phosphates; D010743:Phospholipids; D010972:Platelet Activating Factor