Brown E M, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger M A, Lytton J, Hebert S C
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Nature. 1993 Dec 9;366(6455):575-80. doi: 10.1038/366575a0.
Maintenance of a stable internal environment within complex organisms requires specialized cells that sense changes in the extracellular concentration of specific ions (such as Ca2+). Although the molecular nature of such ion sensors is unknown, parathyroid cells possess a cell surface Ca(2+)-sensing mechanism that also recognizes trivalent and polyvalent cations (such as neomycin) and couples by changes in phosphoinositide turnover and cytosolic Ca2+ to regulation of parathyroid hormone secretion. The latter restores normocalcaemia by acting on kidney and bone. We now report the cloning of complementary DNA encoding an extracellular Ca(2+)-sensing receptor from bovine parathyroid with pharmacological and functional properties nearly identical to those of the native receptor. The novel approximately 120K receptor shares limited similarity with the metabotropic glutamate receptors and features a large extracellular domain, containing clusters of acidic amino-acid residues possibly involved in calcium binding, coupled to a seven-membrane-spanning domain like those in the G-protein-coupled receptor superfamily.
在复杂生物体中维持稳定的内部环境需要专门的细胞来感知特定离子（如Ca2+）细胞外浓度的变化。尽管这种离子传感器的分子本质尚不清楚，但甲状旁腺细胞拥有一种细胞表面Ca(2+)传感机制，该机制也能识别三价和多价阳离子（如新霉素），并通过磷酸肌醇代谢和胞质Ca2+的变化与甲状旁腺激素分泌的调节相偶联。后者通过作用于肾脏和骨骼来恢复正常血钙水平。我们现在报告从牛甲状旁腺中克隆出编码细胞外Ca(2+)传感受体的互补DNA，其药理和功能特性与天然受体几乎相同。这种新的约120K受体与促代谢型谷氨酸受体有有限的相似性，其特征是有一个大的细胞外结构域，包含可能参与钙结合的酸性氨基酸残基簇，与G蛋白偶联受体超家族中的七跨膜结构域相连。
