Arachidonate Metabolism in Cultured Bovine Pericardial Mesothelial Cells with Special Reference to Prostacyclin Production in Response to Thrombin, Histamine and Bradykinin

Abstract

Cultured mesothelial cells from bovine pericardium actively metabolize arachidonic acid, and the metabolites were identified as 6-keto prostaglandin (PG)F_1α, PGE₂ and monohydroxy acid in thin-layer and high-performance liquid chromatography. Although the monohydroxy acid was tentatively identified as either one of 5-, 8- or 11- hydroxyeicosatetraenoic acid, the isomeric form of the compound was not clearly determined. Quantitative measurement of 6-keto PGF_1α production by the cells in response to the stimulation with Ca ionophore A23187 or exogenous arachidonic acid disclosed the production of prostacyclin almost comparable to that by vascular endothelial cells. Cultured mesothelial cells produced a substantial amount of 6-keto PGF_1α in response to thrombin, histamine and bradykinin, as well. Receptor subtypes responsible for the actions of histamine and bradykinin were identified as H₁-and B₂-receptors, respectively, which are the same receptor subtypes involved in the stimulation of endothelial 6-keto PGF_1α production by these compounds.
Mesothelial cells virtually account for the arachidonate metabolism in the pericardium and the eicosanoids generated by the pericardium, with the access to coronary arteries and myocardium on the epicardial surface, may play an important role in the regulation of cardiac function.