Effects of prostaglandin E2 and indomethacin on 25-hydroxyvitamin D3-1 alpha-hydroxylase activity in isolated kidney cells of normal and streptozotocin-induced diabetic rats.

The effects of prostaglandin E2 (PGE2) (1 microM) and indomethacin (IN) (20 microM) on 1,25 dihydroxyvitamin D3 production were studied in renal cell suspensions isolated from control, streptozotocin-induced diabetic, and insulin-treated diabetic rats. Renal cortex cells were isolated by enzymatic digestion, and preincubated for 30 min at 37 degrees C with the appropriate additive(s) followed by a 1 h incubation with 8 nM 25-hydroxyvitamin D3 in serum-free medium. Radioactivity incorporated into that fraction of the cell suspension extract co-eluting with synthetic 1,25-dihydroxyvitamin D3 on high pressure liquid chromatography was determined. All animals were raised for 5 weeks on a vitamin D-deficient diet. Isolated kidney cells from vitamin D-deficient rats showed dose-dependent response of 1,25 dihydroxyvitamin D3 production to PGE2. Cells from control animals demonstrated a stimulatory effect of PGE2 (P less than 0.05) and a suppressive effect of IN (P less than 0.01) on 1,25 dihydroxyvitamin D3 production. In contrast, cells from diabetic rat kidneys failed to respond to these agents, alterations which were reversed by insulin treatment. The accumulated data suggest that depressed synthesis of 1,25 dihydroxyvitamin D3 previously observed in the experimental diabetic rat is due, at least in part, to an impaired production and response to PGE2-like prostaglandins.