Yamaguchi D T, Hahn T J, Iida-Klein A, Kleeman C R, Muallem S
J Biol Chem. 1987 Jun 5;262(16):7711-8.
Changes in free cytosolic calcium were measured in UMR-106 cells in response to parathyroid hormone (PTH) stimulation. Bovine PTH-(1-34) induced an increase in [Ca2+]i with the contour of the rise in [Ca2+]i occurring in three successive phases: a rapid increase in [Ca2+]i occurring within seconds, rapid decrement in [Ca2+]i to near-resting levels within 1 min, and slow increment in [Ca2+]i. Phase one and phase three increases in [Ca2+]i were dependent on medium calcium. The phase one rise in [Ca2+]i was inhibitable by the calcium channel blockers lanthanum and verapamil. Only the phase one rise in [Ca2+]i was blocked by preincubation of the cells with the phorbol ester, phorbol 12-myristate 13-acetate. This channel was also blocked when cellular cAMP levels were increased prior to PTH stimulation. The phase two decrement of [Ca2+]i was due to the rapid inactivation of the phase one calcium channel. The phase three rise in [Ca2+]i was mediated by cellular cAMP levels. This cAMP-dependent Ca2+ channel was insensitive to pretreatment of the cells with phorbol diesters and showed low sensitivity to Ca2+ channel blockers. It is concluded that UMR-106 cells respond to PTH stimulation by the activation of a cAMP-independent Ca2+ channel. This channel rapidly inactivates. The subsequent PTH-dependent increase in cellular cAMP is followed by activation of a cAMP-dependent Ca2+ channel resulting in a slow rise in [Ca2+]i.
在UMR-106细胞中测量了游离胞质钙的变化，以响应甲状旁腺激素（PTH）刺激。牛PTH-(1-34)诱导细胞内钙离子浓度（[Ca2+]i）升高，[Ca2+]i升高的轮廓呈三个连续阶段：数秒内[Ca2+]i迅速升高，1分钟内[Ca2+]i迅速下降至接近静息水平，以及[Ca2+]i缓慢升高。第一阶段和第三阶段[Ca2+]i的升高依赖于培养基中的钙。第一阶段[Ca2+]i的升高可被钙通道阻滞剂镧和维拉帕米抑制。只有第一阶段[Ca2+]i的升高可被佛波酯（佛波醇12-肉豆蔻酸酯13-乙酸酯）预处理细胞所阻断。当在PTH刺激前细胞内cAMP水平升高时，该通道也被阻断。第二阶段[Ca2+]i的下降是由于第一阶段钙通道的快速失活。第三阶段[Ca2+]i的升高由细胞内cAMP水平介导。这种cAMP依赖性钙通道对佛波酯预处理细胞不敏感，对钙通道阻滞剂敏感性较低。结论是，UMR-106细胞通过激活一种不依赖cAMP的钙通道对PTH刺激作出反应。该通道迅速失活。随后PTH依赖性细胞内cAMP的增加伴随着一种cAMP依赖性钙通道的激活，导致[Ca2+]i缓慢升高。
