Relative contribution of the de novo and remodelling pathways to the synthesis of platelet-activating factor in brain areas and during ischemia

Abstract

Two distinct pathways for the synthesis of platelet-activating factor (PAF) have been demonstrated in the nervous tissue. This potent lipid mediator is involved in physiological and pathological processes. The relative contribution of the two pathways to its synthesis during various conditions needs to be defined, thus the activities of the enzymes directly responsible for PAF synthesis, PAF-synthesizing phosphocholinetransferase (PAF-PCT) and lyso-PAF acetlytransferase (lyso-PAF AcT), have been assayed in rat brain areas. The former catalyses the last reaction of the de novo pathway and the latter that of the remodelling one. PAF-PCT activity was always more elevated thant hat of lyso PAF AcT. No differences were observed among different brain areas when enzyme activities were assayed in their homogenates. In microsomes, the highest PAF-PCT activity was found in cerebellum whereas lyso-PAF AcT activity was greater in cerebellum and in hippocampus than in the other brain areas. The activity of PAF-synthesizing enzymes was also studied in the gerbil during ischemia and reperfusion. After 6 min from bilateral occlusion of the carotid arteries, a significant increase of lyso-PAF AcT activity was observed in the hippocampus. This enzyme activity remained relatively high up to 3 days after reperfusion whereas, in other brain areas it reached basal levels much earlier. Since it has been shown that the PAF levels increase in the brain of animals during ischemia, these results suggest that the remodelling pathway may provide an important contribution to its synthesis particularly in the hippocampus, where a selective neuronal death is observed. In this area during reperfusion, a further contribution to PAF synthesis might be also provided by the de novo pathway.