Regulation of 25-hydroxy-vitamin D-1 alpha-hydroxylase in chick isolated renal tubules: effects of prostaglandin E2, frusemide and acetylsalicylic acid.

1. Isolated renal tubules were prepared from vitamin D-deficient chicks. The effects of added prostaglandin E2 (PGE2) and agents which modify prostaglandin metabolism on the metabolism of 25-hydroxy-vitamin D3 were studied. 2. Frusemide (0.1 mmol/l) raised the prostaglandin E (PGE) content of the tubule incubation medium; it significantly increased 1,25-dihydroxy-vitamin D3 [1,25-(OH)2D3] production from 25-hydroxy-vitamin D3 [25-(OH)D3] and significantly inhibited the net production of 24,25-dihydroxy-vitamin D3 [24,25-(OH)2D3]. 3. Acetylsalicylic acid (aspirin; 0.1 mmol/l) decreased the PGE content of the tubule incubation medium and significantly inhibited 1,25-(OH)2D3 production. 4. In the presence of 1,25-(OH)2D3, 4 h exposure of tubules from vitamin D-deficient chicks to concentrations of PGE2 between 2.8 X 10(-6) and 2.8 X 10(-8) mol/l significantly enhanced 1,25-(OH)2D3 production. 5. It is concluded that, in view of the effects of modulation of endogenous prostaglandin levels by frusemide in aspirin, and the stimulatory effect of exogenous PGE2, prostaglandins should be considered potential regulators of the renal 25-hydroxy-vitamin D-1 alpha-hydroxylase [25-(OH)D-1 alpha-hydroxylase] enzyme.