Actions of parathyroid hormone and 1,25-dihydroxycholecalciferol on citrate decarboxylation in osteoblast-like bone cells differ in calcium requirement and in sensitivity to trifluoperazine.
The actions of PTH in OB bone cells appear to involve both calcium and cAMP. At present little information exists regarding the relationship, if any, between these two putative second messengers of hormone action in bone cells. In this report the molecular role of calcium in the actions of PTH and 1,25(OH)2D3 has been compared, since like PTH, the steroid 1,25(OH)2D3 is a potent bone resorbing hormone that exerts inhibition of citrate decarboxylation in OB cells, but unlike PTH does not activate adenylate cyclase. It was found that 1,25(OH)2D3 could initiate near maximum inhibition of citrate decarboxylation at extracellular calcium levels as low as 0.05 mM, whereas PTH effects began to be apparent only at 0.1 mM calcium, and maximum inhibition of citrate decarboxylation by PTH required 0.5 mM Ca. In addition, PTH-induced decrease in citrate decarboxylation was inhibited by low doses of TFP, an inhibitor of calmodulin and calcium-dependent, phospholipid-sensitive protein kinases, in contrast to 1,25(OH)2D3, whose effects were not reduced by this agent. These results suggest that: (a) the actions of 1,25(OH)2D3 may not be directly dependent on calcium influx; (b) in OB cell response to PTH a relationship probably exists between cAMP and calcium; and (c) this relationship may involve calmodulin, or calcium-dependent protein kinases that can be inhibited by TFP.
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D002951:Citrates / Q000378:metabolism*; D019343:Citric Acid; D000242:Cyclic AMP / Q000378:metabolism; D003653:Decarboxylation; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology
D002951:Citrates; D010281:Parathyroid Hormone; D014268:Trifluoperazine; D019343:Citric Acid; D000242:Cyclic AMP; D002117:Calcitriol; D002118:Calcium