Arachidonic acid metabolism in human trabecular meshwork cells

Abstract

Prostaglandins and other eicosanoids in the trabecular meshwork may play important physiological and pharmacological roles in the aqueous outflow pathway. In the present studies, we employed [14C]-arachidonic acid to explore potentially important pathways for the production of eicosanoids in cultured human trabecular meshwork cells (HTM). In these cells, we demonstrated that prostaglandin E2 (PGE2) and PGF2 alpha are major cyclooxygenase products, with some 6-keto-PGF1 alpha also detected. The amount of radiolabelled PGE2 formed was substantially higher than the PGF2 alpha formed in the early time periods. The amount of PGF2 alpha in the culture media increased at a time when the amount of PGE2 was declining, suggesting a possible metabolic conversion between the prostaglandins. HTM produced a range of products of the lipoxygenase pathway. Products co-eluting with 5, 12, and 15-hydroxyeicosatetraenoic acids (HETEs) were detected, with 12 and 15-HETEs predominating. A large amount of radiolabelled product was detected also in peaks co-eluting with leukotriene B4 (LTB4) and an LTB4 degradation product. Biosynthesis of lipoxygenase products was markedly inhibited by BW 755c and partially inhibited by dexamethasone. These data emphasize that HTM cells are capable of converting arachidonic acid into a wider variety of biologically active products than previously recognized.