Regulation of 25-Hydroxy-Vitamin D-1α-Hydroxylase in Chick Isolated Renal Tubules: Effects of Prostaglandin E2, Frusemide and Acetylsalicylic Acid

Abstract

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 × 10⁻⁶ and 2.8 × 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-1α-hydroxylase [25-(OH)D-1α-hydroxylase] enzyme.