Quamme G, Pfeilschifter J, Murer H
Institute of Physiology, University of Zurich, Switzerland.
Biochim Biophys Acta. 1989 Sep 19;1013(2):166-72. doi: 10.1016/0167-4889(89)90045-1.
Parathyroid hormone increases cellular cAMP, 1,2-diacylglycerol, inositol 1,4,5-trisphosphate and cytosolic Ca2+ concentration ([Ca2+]i) in OK cells. In the present study, we determined the importance of the PTH-dependent increase in [Ca2+]i in the control of sodium-dependent phosphate (Na+/Pi) cotransport. PTH (10(-7) M) results in a transient increase in [Ca2+]i from basal levels of 67 +/- 4 nM to maximal concentrations of 190 +/- 9 nM. The increase in [Ca2+]i was dose-dependent with half-maximal increases at about 5.10(-8) M PTH. These hormone levels were 10(3)-fold higher than that required for half-maximal inhibition of Na+/Pi cotransport. Clamping [Ca2+]i with either intracellular Ca2+ chelators or by ionomycin in the presence of high concentrations of extracellular Ca2+ did not alter PTH-dependent inhibition of Na/Pi cotransport. Nor did indomethacin, an inhibitor of the cyclooxygenase pathway, influence the hormonal inhibition of cotransport. Accordingly, these data suggest that changes in [Ca2+]i and/or activation of the phospholipase A2 and the cyclooxygenase pathways are not involved in signal induction of the PTH-mediated control of Na+/Pi cotransport.
甲状旁腺激素可增加OK细胞中的细胞内环磷酸腺苷（cAMP）、1,2 - 二酰甘油、肌醇1,4,5 - 三磷酸以及胞质钙离子浓度（[Ca2+]i）。在本研究中，我们确定了[Ca2+]i依赖甲状旁腺激素升高在钠依赖性磷酸盐（Na+/Pi）协同转运调控中的重要性。甲状旁腺激素（10(-7) M）可使[Ca2+]i从基础水平的67±4 nM短暂升高至最大浓度190±9 nM。[Ca2+]i的升高呈剂量依赖性，在约5×10(-8) M甲状旁腺激素时达到半数最大升高。这些激素水平比半数最大抑制Na+/Pi协同转运所需水平高10(3)倍。在高浓度细胞外钙离子存在的情况下，用细胞内钙离子螯合剂或离子霉素钳制[Ca2+]i，并不会改变甲状旁腺激素对Na/Pi协同转运的依赖性抑制。环氧化酶途径抑制剂吲哚美辛也不会影响激素对协同转运的抑制作用。因此，这些数据表明，[Ca2+]i的变化和/或磷脂酶A2及环氧化酶途径的激活并不参与甲状旁腺激素介导的Na+/Pi协同转运调控的信号诱导过程。
