Blockade of the renal tubular effects of vitamin D by cycloheximide in the rat.
To further characterize the mechanisms by which 25(OH) vitamin D3 (25(OH)D3) and 1.25(OH)2 vitamin D3 (1,25(OH)2D3) suppress the phosphaturic action of parathyroid hormone (PTH) we have studied the effects of cycloheximide (cyclohex), a protein synthesis inhibitor, on the interaction between PTH and vitamin D metabolites in parathyroidectomized (PTX) rats, both in vivo and in vitro experiments. In clearance studies PTX PTH-infused rats were pretreated with cyclohex 2 h before the administration of vitamin D. In control, PTX PTH-infused rats not pretreated with cyclohex, the administration of 25(OH)D3 and 1,25(OH)2D3 was associated with a fall in fractional excretion of phosphate (CP/CIN) from 0.30 +/- 0.05 to 0.16 +/- 0.02 and from 0.31 +/- 0.05 to 0.13 +/- 0.01 (P less than 0.005) respectively. Cyclohex-pretreated PTX PTH-infused rats failed to respond to both 25(OH)D3 and 1,25(OH)2D3, and CP/CIN, which rose after PTH, remained 0.32 +/- 0.05 and 0.29 +/- 0.03 respectively. In vitro, both 25(OH)D3 and 1,25(OH)2D3 inhibited the PTH-induced activation of adenylate cyclase in the renal isolated membrane fractions. Pretreatment with cyclohex abolished this effect of vitamin D metabolites. These results show that cyclohex blocks the antiphosphaturic effects of both 25(OH)D3 and 1,25(OH)2D3 but does not alter the response to PTH. These findings are consistent with the possibility that the acute renal action of vitamin D depends on de novo synthesis of protein.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002112:Calcifediol / Q000494:pharmacology; D002117:Calcitriol; D003513:Cycloheximide / Q000494:pharmacology*; D007672:Kidney Cortex / Q000201:enzymology; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects*; D008297:Male; D010280:Parathyroid Glands / Q000601:surgery; D010281:Parathyroid Hormone / Q000502:physiology; D010758:Phosphorus / Q000502:physiology; D051381:Rats; D013268:Stimulation, Chemical; D014807:Vitamin D / Q000494:pharmacology*
D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; D003513:Cycloheximide; D000262:Adenylyl Cyclases; D002117:Calcitriol; D002112:Calcifediol