Chang J M, Lai Y H, Tsai J H
Division of Nephrology, Kaohsiung Medical College, Taiwan.
Miner Electrolyte Metab. 1997;23(2):113-20.
Endothelin-1 (ET-1) secretion from bovine parathyroid cells (bPTCs) responds to the changes in extracellular calcium concentrations ([Ca2+]c) and ET-1 inhibits parathyroid hormone (PTH) secretion. However, the effect from the interaction between [Ca2+]e and ET-1 on PTH secretion is unknown. To clarify these issues, a bPTC suspension was used to study the regulation of ET-1 secretion by subtle changes in [Ca2+]e and PTH secretion by the interaction between [Ca2+]e and ET-1. We added [Ca2+]e at varying concentrations, 0.5-2.0 mM, to the bPTC medium to define the relationship between [Ca2+]e and ET-1 secretion and found that the ET-1 secretion was inversely regulated by [Ca2+]e with a low [Ca2+]e stimulating, and a high [Ca2+]e inhibiting ET-1 secretion. It is even suppressed to an undetectable level at a [Ca2+]e of > 1.5 mM. Further, we worked to determine how the interaction between ET-1 and [Ca2+]e influences PTH secretion. ET-1 > or = 10(-10) M, inhibited PTH secretion in a dose-dependent manner and significantly inhibited PTH secretion at a low or normal [Ca2+]e. At an ET-1 concentration of > or = 10(-10) M, the 'calcium-PTH' relation showed significant changes in physiological responses. The effect of ET-1 on intracellular calcium concentrations ([Ca2+]i) of bPTCs was studied using the fura 2 fluorescence method. We found that increasing doses of ET-1 induced a progressive increase in [Ca2+]i of bPTCs. Our results suggest that ET-1 secretion is inversely regulated by [Ca2+]e. ET-1 can inhibit PTH secretion and alter the parathyroid secretion pattern to various calcium stimuli. ET-1 also elevates [Ca2+]i and this may be a part of the intracellular signaling mechanisms involved in the inhibition of PTH secretion from bPTCs.
牛甲状旁腺细胞（bPTCs）分泌的内皮素-1（ET-1）对细胞外钙浓度（[Ca2+]c）的变化有反应，且ET-1抑制甲状旁腺激素（PTH）的分泌。然而，[Ca2+]e与ET-1之间的相互作用对PTH分泌的影响尚不清楚。为了阐明这些问题，我们使用bPTC悬浮液来研究[Ca2+]e的细微变化对ET-1分泌的调节以及[Ca2+]e与ET-1之间的相互作用对PTH分泌的调节。我们向bPTC培养基中添加了浓度在0.5 - 2.0 mM之间变化的[Ca2+]e，以确定[Ca2+]e与ET-1分泌之间的关系，发现ET-1分泌受到[Ca2+]e的反向调节，低[Ca2+]e刺激ET-1分泌，高[Ca2+]e则抑制ET-1分泌。当[Ca2+]e > 1.5 mM时，ET-1分泌甚至被抑制到检测不到的水平。此外，我们致力于确定ET-1与[Ca2+]e之间的相互作用如何影响PTH分泌。ET-1≥10(-10) M时，以剂量依赖方式抑制PTH分泌，并且在低[Ca2+]e或正常[Ca2+]e水平时显著抑制PTH分泌。在ET-1浓度≥10(-10) M时，“钙 - PTH”关系在生理反应上显示出显著变化。我们使用fura 2荧光法研究了ET-1对bPTCs细胞内钙浓度（[Ca2+]i）的影响。我们发现，ET-1剂量增加会导致bPTCs的[Ca2+]i逐渐升高。我们的数据表明，ET-1分泌受到[Ca2+]e的反向调节。ET-1可以抑制PTH分泌，并改变甲状旁腺对各种钙刺激的分泌模式。ET-1还会升高[Ca2+]i，这可能是参与抑制bPTCs分泌PTH的细胞内信号传导机制的一部分。
