Prostaglandin endoperoxide metabolism by bovine cerebral micro vessels

Abstract

Isolated bovine cerebral microvessels were found to contain two prostaglandin endoperoxide-metabolizing activities: prostaglandin H 2-E 2 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 E 2 was favored (about 80% of total prostaglandin products), whereas at higher protein concentrations, in the presence or absence of reduced glutathione, 6-keto-prostaglandin F 1α, the stable breakdown product of prostacyclin, was the major product (40–50% of total). Despite an increase in apparent prostacyclin formation, glutathione-enhanced prostaglandin E 2 production was still evident at protein concentrations exceeding 1 mg/ml. No apparent enzymatic prostaglandin E 2 forming activity was evident in whole cerebral cortex or pial artery homogenates although some GSH-enhanced prostaglandin E 2 formation could be demonstrated in microsomes prepared from these tissues. These findings indicate that prostaglandin E 2 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 E 2 and prostacyclin generated in the microvasculature could participate in the regulation of various functions e.g., regional flow and capillary permeability.