OzEMedicine - Wiki for Australian Emergency Medicine Doctors

see also eicosanoids including prostaglandins

• A soluble substance demonstrated to be released from leukocytes which caused platelet aggreg. (1971), which was confirmed & named PAF;
• Also at this time an antiHT polar renal lipid (APRL) produced by interstitial cells of renal medulla was described, & this was concluded to be identical to PAF in 1979 & was then also synthesised & shown to be AGEPC - a phospholipid.
• PAF actually represents a family of phospholipids & like the eicosanoids including prostaglandins are not stored in cells but synthesised in response to stimulation.

• Precursor is 1-O-alkyl-2-acyl-glycerophosphocholine - a lipid found in high [] in membranes of many cells;
• 1st step: Plipase A2 converts it to lyso-PAF & a FFA (usually arachid.acid)
• 2nd rate-limiting step:
  • lyso-PAF converted to PAF:
    • by acetyl-coA, catalysed by lyso-PAF acetyltransferase;
• Both steps are regulated by Ca availability and stimulated by:
  • Ag-Ab reactions, chemotactic peptides, thrombin, collagen;
  • other autacoids & PAF itself;
• Occurs mainly in platelets, neutrophils, eosinophils, mast cells, monocytes, renal medullary cells, vascular endothelial cells;
• Usually synthesis → release from cell & act on G-protein-coupled receptors but in endothelial cells, it acts i/cellularly;

• Plasma & cytosolic PAF acetylhydrolase forms lyso-PAF which is then converted back to the PAF precursor by an acyltransferase which is inhibited by Ca;

• A potent vasodil. but high [] may → decr. flow due to plat.effect;
• incr. vasc. permeability (1000 hist.) & promotes oedema formation;

• potent plat. aggreg. & release of TXA2;

• PMNL aggregation & release of LT's, lysosomals & superoxide chemotactic for eosinophils, neutrophils, & monocytes;
• incr. neutrophil adherence & diapedesis;

• contracts GIT, uterine, pulm. sm.muscle;
• → delayed (~3D) & prolonged (1-4wks) bronchial hyperreact.
• → incr. mucus prod. & incr. perm. pulm.microvessels;
• → most potent known ulcerogen;

• decr. RBF, decr.GFR, decr. urine volume, decr. Na excretion; incr. vasodil.PG's;

• role in ovulation, implantation & parturition;

• development still in infancy (disc. 1987);
• Triazolobenzodiazepines (eg. alprazolam, triazolam)
• Ginkgolide B (from Ginkgo biloba) - a terpene;
• ? Role in: asthma Rx; anaphylactic shock Rx; contraceptives;