Molecular and functional identification of a Ca2+ (polyvalent cation)-sensing receptor in rat pancreas
Molecular and functional identification of a Ca2+ (polyvalent cation)-sensing receptor in rat pancreas
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DOI：
10.1074/jbc.274.29.20561
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发表时间：
1999-07-16
影响因子：
4.8
通讯作者：
Riccardi, D
中科院分区：
文献类型：
--
作者：
Bruce, JIE;Yang, XS;Riccardi, D
胰液中游离离子 Ca2+ 和碳酸氢盐浓度之间的平衡对于防止碳酸钙结石的形成至关重要。胰腺如何在碱性环境（如胰液）中调节离子组成和 Ca2+ 饱和度水平尚不清楚。由于 Ca2+ 浓度与成石性之间存在紧密的因果关系，并且由于高钙血症被认为是多种胰腺疾病的病因，我们研究了胰腺组织是否表达与最近在甲状旁腺组织中发现的类似的 Ca2+ 感应受体 (CaR)。使用逆转录聚合酶链反应和免疫荧光显微镜，我们证明了大鼠胰腺腺泡细胞、胰管和胰岛中存在 CaR 样分子。功能研究（在分离的腺泡细胞和小叶间导管中测量细胞内游离 Ca2+ 浓度）表明，两种细胞类型都对 CaR 激动剂钆 (Gd3+) 和细胞外 Ca2+ 浓度的变化有反应。我们还通过测量细胞内 pH 值来评估 CaR 刺激对导管生理性 HCO3- 分泌的影响。 Luminal Gd3+ 是 HCO3- 分泌的有效刺激物，与用毛喉素提高细胞内 cAMP 同等有效。这些结果表明，外分泌胰腺中的 CaR 监测胰液中的 Ca2+ 浓度，因此可能参与调节腔内 Ca2+ 的水平，无论是在基础条件下还是在激素刺激期间。这一机制的失败可能导致胰腺结石形成，甚至胰腺炎。
The balance between the concentrations of free ionized Ca2+ and bicarbonate in pancreatic juice is of critical importance in preventing the formation of calcium carbonate stones. How the pancreas regulates the ionic composition and the level of Ca2+ saturation in an alkaline environment such as the pancreatic juice is not known. Because of the tight cause-effect relationship between Ca2+ concentration and lithogenicity, and because hypercalcemia is proposed as an etiologic factor for several pancreatic diseases, we have investigated whether pancreatic tissues express a Ca2+-sensing receptor (CaR) similar to that recently identified in parathyroid tissue. Using reverse transcriptase-polymerase chain reaction and immunofluorescence microscopy, we demonstrate the presence of a CaR-like molecule in rat pancreatic acinar cells, pancreatic ducts, and islets of Langerhans, Functional studies, in which intracellular free Ca2+ concentration was measured in isolated acinar cells and interlobular ducts, show that both cell types are responsive to the CaR agonist gadolinium (Gd3+) and to changes in extracellular Ca2+ concentration. We also assessed the effects of CaR stimulation on physiological HCO3- secretion from ducts by making measurements of intracellular pH. Luminal Gd3+ is a potent stimulus for HCO3- secretion, being equally as effective as raising intracellular cAMP with forskolin, These results suggest that the CaR in the exocrine pancreas monitors the Ca2+ concentration in the pancreatic juice, and might therefore be involved in regulating the level of Ca2+ in the lumen, both under basal conditions and during hormonal stimulation. The failure of this mechanism might lead to pancreatic stone formation and even to pancreatitis.