Factors regulating prostaglandin E 2 biosynthesis in renal cortical tubular cells

Abstract

Prostaglandin synthesis by isolated rat renal cortical tubular cells was studied in vitro with a superfusion system. The cells were introduced in Teflon chambers and intermittently stimulated. The PGE 2 production was measured in the effluent. ANG II (10 −10–10 −6M) induced a dose-dependent increase in PGE 2 synthesis. Saralasin antagonized the response to ANG II. Hyperosmolar mannitol or NaCl and Ca 2+-ionophore A23187 also stimulated PGE 2 synthesis. The PGE 2 response to all stimuli was blocked in Ca 2+-free media containing EGTA. The Ca 2+-channel blocker nifedipine (10 −10–10 −6M) did not significantly inhibit the PGE 2 response to ANG II, hyperosmolar mannitol or NaCl, and A23187, whereas the phospholipase-inhibitors p-bromophenacyl bromide (10 −4M) and chloroquine (10 −4M) inhibited the response. Thus, PGE 2 synthesis in response to these stimuli in rat renal cortical tubular cell is a Ca 2+-dependent process, acting via phospholipases by a mechanism which does not appear to involve voltage-dependent Ca 2+ -channels.