Biosynthesis of platelet activating factor in rabbit polymorphonuclear neutrophils.
The synthesis of platelet activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) was studied in rabbit peritoneal polymorphonuclear neutrophils. Upon stimulation with ionophore A23187 and Ca2+, these cells are able to incorporate [3H]acetate or 1-O-[3H]alkyl-2-lyso-sn-glycero-3-phosphocholine into platelet activating factor. Under the same incubation conditions, however, the cells do not synthesize platelet activating factor from [14C]hexadecanol, which is an immediate precursor of O-alkyl chains in the de novo pathway. In the absence of ionophore, [14C] hexadecanol is incorporated into 1-O-alkyl-2-acyl-sn-glycerol-3-phosphate and subsequently into the 1-O-alkyl-linked choline and ethanolamine phosphoglyceride pools. However, in the presence of ionophore, [14C] hexadecanol incorporation is limited to phosphatidic acid, perhaps due to the inhibition of choline phosphotransferase. These findings provide strong evidence that platelet activating factor is synthesized by a deacylation-reacylation mechanism. Upon stimulation, these cells can utilize both plausible substrates of this pathway to make the final product, while under the same conditions it appears that a key step of the de novo pathway is inhibited.
D000085:Acetates / Q000378:metabolism; D000215:Acylation; D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D005233:Fatty Alcohols / Q000378:metabolism; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000378:metabolism; D011817:Rabbits
D000085:Acetates; D005233:Fatty Alcohols; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D000001:Calcimycin; C005031:cetyl alcohol; D002118:Calcium