Factors regulating prostaglandin E2 biosynthesis in renal cortical tubular cells

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 PGE2 production was measured in the effluent. ANG II (10(-10)-10(-6)M) induced a dose-dependent increase in PGE2 synthesis. Saralasin antagonized the response to ANG II. Hyperosmolar mannitol or NaCl and Ca2+-ionophore A23187 also stimulated PGE2 synthesis. The PGE2 response to all stimuli was blocked in Ca2+-free media containing EGTA. The Ca2+-channel blocker nifedipine (10(-10)-10(-6)M) did not significantly inhibit the PGE2 response to ANG II, hyperosmolar mannitol or NaCl, and A23187, whereas the phospholipase-inhibitors p-bromophenacyl bromide (10(-4)M) and chloroquine (10(-4)M) inhibited the response. Thus, PGE2 synthesis in response to these stimuli in rat renal cortical tubular cell is a Ca2+-dependent process, acting via phospholipases by a mechanism which does not appear to involve voltage-dependent Ca2+-channels.