Ray J M, Squires P E, Curtis S B, Meloche M R, Buchan A M
Department of Physiology, University of British Columbia, Vancouver V6T 1Z3, Canada.
J Clin Invest. 1997 May 15;99(10):2328-33. doi: 10.1172/JCI119413.
The presence of the extracellular calcium-sensing receptor on human antral gastrin cells was investigated. Reverse transcription PCR using mRNA isolated from gastrin cell- enriched cell cultures identified a product with a sequence identical to part of the human parathyroid-secreting cell calcium-sensing receptor. Immunocytochemistry with an antibody to the extracellular region of the receptor immunostained all gastrin cells (but not mucin or somatostatin cells), and detected appropriate-sized bands in Western blots of whole cell lysates. Increasing extracellular calcium levels from 0.5 to 9 mM stimulated gastrin release in a concentration-dependent manner, with maximal release obtained at 7.2 mM. A known agonist of the calcium receptor, spermine also stimulated gastrin release. Microfluorimetry of identified gastrin cells demonstrated that increasing extracellular calcium resulted in an initial rapid rise in intracellular calcium followed by a plateau level that returned to basal levels immediately after removal of the elevated calcium. The traces were consistent with activation of a receptor-mediated mechanism rather than a concentration-dependent influx of calcium. In conclusion, these data indicate that G cells express the calcium-sensing receptor, and that activation of the receptor may explain the acid rebound phenomenon associated with calcium-containing antacid preparations.
研究了人胃窦胃泌素细胞上细胞外钙敏感受体的存在情况。使用从富含胃泌素细胞的细胞培养物中分离的mRNA进行逆转录PCR,鉴定出一种产物,其序列与人甲状旁腺分泌细胞钙敏感受体的一部分相同。用针对该受体细胞外区域的抗体进行免疫细胞化学检测,结果显示所有胃泌素细胞均呈免疫染色阳性(但粘蛋白或生长抑素细胞未染色),并且在全细胞裂解物的蛋白质免疫印迹中检测到了大小合适的条带。将细胞外钙水平从0.5 mM提高到9 mM,以浓度依赖的方式刺激胃泌素释放,在7.2 mM时释放量达到最大。钙受体的一种已知激动剂精胺也能刺激胃泌素释放。对已鉴定的胃泌素细胞进行微量荧光测定表明,细胞外钙增加会导致细胞内钙最初迅速升高,随后达到一个平台期,在去除升高的钙后立即恢复到基础水平。这些记录结果与受体介导机制的激活一致,而不是与钙的浓度依赖性内流一致。总之,这些数据表明G细胞表达钙敏感受体,并且该受体的激活可能解释了与含钙抗酸制剂相关的酸反跳现象。