Dockray Graham J, Moore Andy, Varro Andrea, Pritchard D Mark
Departments of Cell and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Curr Gastroenterol Rep. 2012 Dec;14(6):453-9. doi: 10.1007/s11894-012-0293-1.
C-terminally amidated gastrins act at cholecystokinin-2 receptors (CCK2R), which are normally expressed by gastric parietal and enterochromaffin-like (ECL) cells and smooth muscle; there is also extensive expression in the CNS where the main endogenous ligand is cholecystokinin. A variety of neoplasms express CCK2R, or splice variants, including neuroendocrine, pancreatic, medullary thyroid and lung cancers. Other products of the gastrin gene (progastrin, the Gly-gastrins) may stimulate cell proliferation but are not CCK2R ligands. Depending on the cell type, stimulation of CCK2R evokes secretion, increases proliferation and cell migration, inhibits apoptosis, and controls the expression of various genes. These effects are mediated by increased intracellular calcium and activation of protein kinase C, MAPkinase and other protein kinase cascades. There has been recent progress in developing CCK2R ligands that can be used for imaging tumours expressing the receptor. New antagonists have also been developed, and there is scope for using these for suppression of gastric acid and for treatment of neuroendocrine and other CCK2R-expressing tumours.
C 末端酰胺化胃泌素作用于胆囊收缩素 2 型受体（CCK2R），该受体通常由胃壁细胞、肠嗜铬样（ECL）细胞和平滑肌表达；在中枢神经系统中也有广泛表达，其中主要的内源性配体是胆囊收缩素。多种肿瘤表达 CCK2R 或其剪接变体，包括神经内分泌癌、胰腺癌、甲状腺髓样癌和肺癌。胃泌素基因的其他产物（前胃泌素、甘氨酸 - 胃泌素）可能刺激细胞增殖，但不是 CCK2R 配体。根据细胞类型不同，CCK2R 的刺激可引起分泌、增加增殖和细胞迁移、抑制细胞凋亡，并控制各种基因的表达。这些效应是由细胞内钙增加以及蛋白激酶 C、丝裂原活化蛋白激酶（MAP 激酶）和其他蛋白激酶级联反应的激活介导的。最近在开发可用于对表达该受体的肿瘤进行成像的 CCK2R 配体方面取得了进展。还开发了新的拮抗剂，并且有将这些拮抗剂用于抑制胃酸分泌以及治疗神经内分泌肿瘤和其他表达 CCK2R 的肿瘤的空间。
