BONE REMODELING SIGNALED BY A DIHYDROPYRIDINE-SENSITIVE AND PHENYLALKYLAMINE-SENSITIVE CALCIUM-CHANNEL
BONE REMODELING SIGNALED BY A DIHYDROPYRIDINE-SENSITIVE AND PHENYLALKYLAMINE-SENSITIVE CALCIUM-CHANNEL
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DOI：
10.1073/pnas.86.8.2957
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发表时间：
1989-04-01
影响因子：
11.1
通讯作者：
SNYDER, SH
中科院分区：
文献类型：
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作者：
GUGGINO, SE;LAJEUNESSE, D;SNYDER, SH
单通道记录显示成骨细胞钙通道与成骨样骨肉瘤细胞中的钙拮抗剂受体结合位点相关。通过使用全细胞电流记录，我们现在表明，该通道是由二氢吡啶钙激动剂药物BAY K 8644刺激。这些通道的生理相关性是显而易见的，从立体选择性，有效抑制甲状旁腺素刺激的钙摄入成骨细胞样细胞培养的去甲氧基维拉帕米，苯烷基胺钙拮抗剂。BAY K 8644可刺激这些细胞分泌骨基质蛋白骨钙素，去甲氧基维拉帕米和尼群地平可阻断这种分泌。该通道在完整动物骨重塑中的作用的证据来自于用BAY K 8644观察到的胎鼠骨的骨吸收增强和去甲氧基维拉帕米对骨吸收的立体选择性、强效阻断。
An osteoblast calcium channel demonstrated by single channel recordings is associated with calcium antagonist receptor binding sites in osteoblast-like osteosarcoma cells. By using whole cell current recordings we now show that this channel is stimulated by the dihydropyridine calcium agonist drug BAY K 8644. A physiological relevance of these channels is apparent from the stereoselective, potent inhibition of parathyroid hormone-stimulated calcium uptake into osteoblast-like cells in culture by desmethoxyverapamil, a phenylalkylamine calcium antagonist. Secretion by these cells of the bone matrix protein osteocalcin is stimulated by BAY K 8644 and blocked by desmethoxyverapamil and nitrendipine. Evidence for a role of this channel in bone remodeling in intact animals comes from enhanced bone resorption in fetal rat bones observed with BAY K 8644 and stereoselective, potent blockade of resorption by desmethoxyverapamil.