Prostaglandin endoperoxide metabolism by bovine cerebral microvessels

Abstract

Isolated bovine cerebral microvessels were found to contain two prostaglandin endoperoxide-metabolizing activities: prostaglandin H2-E2 isomerase and prostacyclin synthetase. At low tissue protein concentrations (i.e., less than 1 mg/ml) and in the presence of reduced glutathione, formation of prostaglandin E2 was favored (about 80% of total prostaglandin products), whereas at higher protein concentrations, in the presence or absence of reduced glutathione, 6-keto-prostaglanding F1 alpha, the stable breakdown product of prostacyclin, was the major product (40-50% of total). Despite an increase in apparent prostacyclin formation, glutathione-enhanced prostaglandin E2 production was still evident at protein concentrations exceeding 1 mg/ml. No apparent enzymatic prostaglandin E2 forming activity was evident in whole cerebral cortex or pial artery homogenates although some GSH-enhanced prostaglandin E2 formation could be demonstrated in microsomes prepared from these tissues. These findings indicate that prostaglandin E2 formation is a dominant enzymatic endoperoxide-metabolizing activity in microvessels, and that this pathway may be primarily localized to the microvasculature. However, they also indicate that enzyme/substrate ratios and endogenous cofactor availability may affect the outcome of endoperoxide metabolism in the bovine cerebral microvasculature, Prostaglandin E2 and prostacyclin generated in the microvasculature could participate in the regulation of various functions, e.g., regional flow and capillary permeability.