Effect of PTH and 1,25(OH)2D3 on renal 25(OH)D3 metabolism, adenylate cyclase, and protein kinase.
The purpose of these studies was to characterize the action of PTH and 1,25(OH)2D3 on the renal metabolism of 25(OH)D3 to 1,25(OH)2D3 and 24,25(OH)2D3. Renal metabolism of 25(OH)D3, adenylate cyclase, and protein kinase activity were measured using isolated renal slices from rats fed a vitamin D-deficient, low-calcium diet and thyroparathyroidectomized. PTH added to renal slices for 4 h in vitro maximally increased 1,25(OH)2D3 production by 67% and decreased 24,25(OH)2D3 production by 24% over the concentration range 0.05-5.0 U/ml. Parathyroid hormone (PTH) (0.05 U/ml) added to renal slices for 5 min produced a significant increase in tissue cAMP and a near-maximal increase in cAMP-dependent protein kinase activity. Preincubation of renal slices with 50 nM 1,25(OH)2D3 decreased renal 1,25(OH)2D3 production by 26% and increased 24,25(OH)2D3 production by 55%. 1,25(OH)2D3 also blocked the effect of PTH (5.0 U/ml) on renal 25(OH)D3 metabolism. However, PTH-stimulated adenylate cyclase and protein kinase activity was not blocked by preincubation with 1,25(OH)2D3. These studies demonstrate that PTH may act directly on the kidney to modulate renal 25(OH)D3 metabolism and that this action can be inhibited by 1,25(OH)2D3. This inhibition by 1,25(OH)2D3 occurs at a site distal to or separate from PTH-stimulated protein kinase activity.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002112:Calcifediol / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D019379:Teriparatide
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D000242:Cyclic AMP; D011494:Protein Kinases; D000262:Adenylyl Cyclases; D002117:Calcitriol; D002112:Calcifediol