Suzuki M, Kurihara S, Kawaguchi Y, Sakai O
Second Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Am J Physiol. 1991 May;260(5 Pt 2):F757-63. doi: 10.1152/ajprenal.1991.260.5.F757.
Vitamin D metabolites exert both acute and chronic influences on proximal tubule function. To further evaluate vitamin D action on the kidney, we examined the immediate effects of vitamin D metabolites on cytoplasmic calcium ion concentration [( Ca2+]i), using fura-2 and patch-clamp method in cultured proximal straight tubule cells of rabbit kidney. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] and 25-hydroxyvitamin D3 [25(OH)D3] evoked a transient rise in [Ca2+]i, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] caused a sustained rise in [Ca2+]i; all effects were dose dependent. [Ca2+]i transient, evoked by 1,25(OH)2D3 alone, was abolished in Ca(2+)-free media. Pretreatment of cells in Ca(2+)-free media with caffeine (4 mM) or ryanodine (1 microM) to deplete Ca2+ store of endoplasmic reticulum or with TMB-8 (5 mM) to block Ca2+ release from storage blunted the effect of 25(OH)D3 on [Ca2+]i but not of 24,25(OH)2D3. Data were also supported by activities of Ca-dependent K channel and show that these three vitamin D metabolites in pharmacological doses increase [Ca2+]i of proximal tubule cells from different sources.
维生素D代谢产物对近端肾小管功能有急性和慢性影响。为了进一步评估维生素D对肾脏的作用，我们采用fura-2和膜片钳技术，在培养的兔肾近端直小管细胞中研究了维生素D代谢产物对细胞质钙离子浓度[Ca2+]i的即时影响。1,25-二羟基维生素D3[1,25(OH)2D3]和25-羟基维生素D3[25(OH)D3]引起[Ca2+]i短暂升高，而24,25-二羟基维生素D3[24,25(OH)2D3]则导致[Ca2+]i持续升高；所有这些作用均呈剂量依赖性。单独由1,25(OH)2D3引起的[Ca2+]i短暂升高在无钙培养基中消失。在无钙培养基中用咖啡因（4 mM）或雷诺丁（1 microM）预处理细胞以耗尽内质网的Ca2+储存，或用TMB-8（5 mM）阻断Ca2+从储存库的释放，可减弱25(OH)D3对[Ca2+]i的作用，但不影响24,25(OH)2D3的作用。钙离子依赖性钾通道的活性数据也支持了这一点，表明这三种药理剂量的维生素D代谢产物可增加不同来源近端小管细胞的[Ca2+]i。
