Larsson R, Akerström G, Gylfe E, Johansson H, Ljunghall S, Rastad J, Wallfelt C
Biochim Biophys Acta. 1985 Nov 20;847(2):263-9. doi: 10.1016/0167-4889(85)90029-1.
The effects of K+ and the Ca2+ channel blocker D-600 on parathyroid hormone (PTH) release and cytoplasmic Ca2+ activity (Ca2+i) were measured at different Ca2+ concentrations in dispersed parathyroid cells from normal cattle and from patients with hyperparathyroidism. When the extracellular Ca2+ concentration was raised within the 0.5-3.0 mM range Ca2+i increased and PTH secretion was inhibited. There was also a stimulatory effect of Ca2+ on secretion as indicated by a parallel decrease of Ca2+i and PTH release when extracellular Ca2+ was reduced to less than 25 nM. Addition of 30-50 mM K+ stimulated PTH release and lowered Ca2+i. The effect of K+ was less pronounced in the human cells with a decreased suppressability of PTH release. The Ca2+ channel blocker D-600 had no effect on Ca2+i and PTH release in the absence of extracellular Ca2+. However, at 0.5-1.0 mM Ca2+, D-600 increased Ca2+i and inhibited PTH release, whereas the opposite effects were obtained at 3.0 mM Ca2+. The transition from inhibition to stimulation occurred at a higher Ca2+ concentration in the human cells and the right-shift in the dose-effect relationship for Ca2+-inhibited PTH release tended to be normalized by D-600. It is suggested that K+ stimulates PTH release by increasing the intracellular sequestration of Ca2+ and that the reduced response in the parathyroid human cells is due to the fact that Ca2+i already is lowered. D-600 appears to have both Ca2+ agonistic and antagonistic actions in facilitating and inhibiting Ca2+ influx into the parathyroid cells at low and high concentrations of extracellular Ca2+, respectively. D-600 and related drugs are considered potentially important for the treatment of hyperparathyroidism.
在来自正常牛和甲状旁腺功能亢进患者的分散甲状旁腺细胞中，于不同钙离子浓度下测定了钾离子（K⁺）和钙离子通道阻滞剂D - 600对甲状旁腺激素（PTH）释放及细胞质钙离子活性（Ca²⁺i）的影响。当细胞外钙离子浓度在0.5 - 3.0 mM范围内升高时，Ca²⁺i增加且PTH分泌受到抑制。当细胞外钙离子降至低于25 nM时，Ca²⁺i和PTH释放平行下降，这也表明钙离子对分泌有刺激作用。添加30 - 50 mM K⁺可刺激PTH释放并降低Ca²⁺i。在人类细胞中，K⁺的作用不太明显，PTH释放的抑制性降低。在无细胞外钙离子时，钙离子通道阻滞剂D - 600对Ca²⁺i和PTH释放无影响。然而，在0.5 - 1.0 mM钙离子浓度下，D - 600增加Ca²⁺i并抑制PTH释放，而在3.0 mM钙离子浓度下则得到相反的效果。在人类细胞中，从抑制到刺激的转变发生在更高的钙离子浓度下，并且D - 600倾向于使钙离子抑制PTH释放的剂量 - 效应关系的右移正常化。提示K⁺通过增加细胞内钙离子的螯合来刺激PTH释放，而人类甲状旁腺细胞反应降低是由于Ca²⁺i已经降低。在低和高细胞外钙离子浓度下，D - 600分别在促进和抑制钙离子流入甲状旁腺细胞方面似乎具有钙离子激动和拮抗作用。D - 600及相关药物被认为对甲状旁腺功能亢进的治疗可能具有重要意义。
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