Metabolism of platelet activating factor (PAF) by rabbit renal homogenates

Rabbit renal cortical slices convert added (alkyl-3H)-PAF to metabolites that cochromatograph with lyso-PAF and alkyl-acyl glycerophosphocholine (AAGPC) and to a tritiated nonpolar metabolite that is the principal product recovered from the tissues. Rabbit renal cortical homogenates convert mixtures of (alkyl-3H)-PAF and (choline-14C)-PAF to products that cochromatograph with lyso-PAF and with AAGPC and to a tritiated nonpolar and a 14C-labeled polar metabolite. Formation of the latter products follow parallel time courses; they are the principal species present after extended incubation (30 min). Enzymatic capacity for formation of these metabolites is concentrated in the microsomal fraction (100,000 x g pellet). Their formation by washed microsomes does not require the addition of cofactors, but their rate of formation is enhanced in the presence of high concentrations of Ca++ (1mM) and abolished by EDTA (1.25mM) or EGTA (1.25mM). Formation of the polar metabolite does not appear to be due to phospholipase C or D activity. Its formation is not enhanced by addition of glutathione or 2-amino-6,7-dimethyl-tetrahydropteridine, cofactors that support oxidative dealkylation of alkyl ether phospholipids in other tissues. Conversion of PAF to final products other than AAGPC appears to be a significant pathway for disposition of this substance in rabbit kidney