The regulation and role of prostaglandin biosynthesis in cultured bovine glomerular endothelial cells.

Abstract

The experiments described in this article were designed to investigate the regulation of, and functional response to, prostaglandin (PG) synthesis in cultured bovine glomerular endothelial cells. Glomerular endothelial cells in culture synthesized PGE2 much greater than PGF2 alpha greater than thromboxane A2 greater than PGI2 in the presence of 30 microM arachidonate. Basal levels of PGE2 synthesis in these cells were one sixth less than that of bovine mesangial cells. PGE2 synthesis was time dependent and required the continuous presence of serum. Moreover, PGE2 synthesis was regulated by phospholipase A2 as shown by ionomycin-stimulated PGE2 accumulation as well as by bradykinin- and thrombin-stimulated PGE2 accumulation. Even though acidic fibroblast growth factor and heparin were required to support glomerular endothelial cell growth in culture, these agents downregulated PGE2 synthesis. PG endoperoxide synthase activity, as shown by arachidonate-stimulated PGE2 accumulation, also regulated PGE2 synthesis. PGE2 and PGF2 alpha, as well as thromboxane A2 and PGI2 mimetics (1 microM) evoked mitogenesis in quiescent glomerular endothelial cells. PGE2 and PGF2 alpha were most potent, and threshold doses of these PG were 10 nM. These data suggest that glomerular endothelial cells are similar to other microvascular endothelial cells in their regulation of PG synthesis and that, under physiological conditions, the proliferation of glomerular endothelial cells might be regulated by PG in an autocrine or paracrine fashion.