STUDIES ON A CALCIUM SENSING RECEPTOR

Brown和他的同事(《自然》1993)克隆了一种新的钙敏感 受体(CAR)是G蛋白偶联受体的成员 在结构上类似于代谢性谷氨酸受体的超家族。 CAR在有限的细胞类型中表达，包括肾脏， 脑、甲状腺C细胞，尤其是甲状旁腺细胞。 家族性人类遗传性疾病中发现的CAR突变 低血钙性低血钙症为生理学提供了强有力的证据 受体在钙敏感和调节中的重要性 细胞外钙离子对甲状旁腺激素分泌的影响 很特别。我们正在研究受体结构的几个方面 和功能。我们已经将多克隆抗血清提纯为几种合成的 与大胞外域序列相对应的多肽。 这些都识别蛋白质印迹上的受体，应该对 各种各样的研究。单克隆抗体的发展是 计划的长期目标是用作 颈部探查失败患者的甲状旁腺肿瘤。我们是 也研究了受体与G蛋白的偶联 通过定义G的正常补体 甲状旁腺细胞中的蛋白质α亚基。

Brown and colleagues (Nature 1993) have cloned a novel calcium-sensing receptor (CaR) which is a member of the G protein-coupled receptor superfamily similar in structure to the metabotropic glutamate receptors. The CaR is expressed in a limited range of cell types including kidney, brain, thyroid C cells, and most prominently parathyroid cells. Mutations in the CaR identified in the human genetic disorder familial hypocalciuric hypocalcemia provide strong evidence for the physiologic importance of the receptor in calcium sensing generally and in regulation of parathyroid hormone secretion by extracellular ionized calcium in particular. We are studying several aspects of the receptor's structure and function. We have raised polyclonal antisera to several synthetic peptides corresponding to sequences in the large extracellular domain. These recognized the receptor on western blots and should be useful for a wide variety of studies. Development of monoclonal antibodies is planned with the long-range goal of being used as imaging reagents for parathyroid tumors in patients with failed neck explorations. We are also studying the coupling of the receptor to G proteins using transfection techniques, and by defining the normal complement of G protein alpha subunits in parathyroid cells.