paf
Platelet activating factor
Introduction:
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.
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Biosynthesis:
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:
Both steps are regulated by Ca availability and stimulated by:
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;
Inactivation of PAF:
Pharmacology of PAF:
CVS:
Platelets:
Leukocytes:
PMNL aggregation & release of LT's, lysosomals & superoxide chemotactic for eosinophils, neutrophils, & monocytes;
incr. neutrophil adherence & diapedesis;
Sm.muscle:
contracts GIT, uterine, pulm. sm.muscle;
→ delayed (~3D) & prolonged (1-4wks) bronchial hyperreact.
→ incr. mucus prod. & incr. perm. pulm.microvessels;
→ most potent known ulcerogen;
Kidney:
Reproduction:
PAF Receptor Antagonists:
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;
paf.txt · Last modified: 2008/09/23 00:18 (external edit)