Individual Subtypes of Enteroendocrine Cells in the Mouse Small Intestine Exhibit Unique Patterns of Inositol 1,4,5-trisphosphate Receptor Expression
Individual Subtypes of Enteroendocrine Cells in the Mouse Small Intestine Exhibit Unique Patterns of Inositol 1,4,5-trisphosphate Receptor Expression
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DOI：
10.1177/002215540405200106
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发表时间：
2004-01
影响因子：
3.2
通讯作者：
Songyan Wang;Jianfeng Liu;Lin Li;B. Wice
中科院分区：
文献类型：
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作者：
Songyan Wang;Jianfeng Liu;Lin Li;B. Wice
肠内分泌细胞是肠上皮细胞的复杂群体，其激素在调节胃肠道和整个动物生理学中发挥着关键作用。根据单个细胞产生的主要激素，肠内分泌细胞有许多亚群。细胞内钙在调节激素释放中起着至关重要的作用。肌醇 1,4,5-三磷酸 (IP3) 受体调节许多内分泌和兴奋细胞中内质网衍生的钙储存的钙动员，并在肠道中表达。然而，表达这些受体的肠内分泌细胞的具体亚型尚未报道。免疫组织化学 (IHC) 研究表明，肠内分泌细胞不表达可检测水平的 2 型 IP3 受体，而几乎所有产生嗜铬粒蛋白 A 和/或血清素的肠内分泌细胞都表达 1 型和 3 型 IP3 受体。相反，产生葡萄糖依赖性促胰岛素多肽、胰高血糖素样肽-1、胆囊收缩素或生长抑素的肠内分泌细胞不表达可检测水平的任何IP3受体。产生 P 物质或促胰液素的肠内分泌细胞亚群表达 1 型（分别为 33% 或 18%）和 3 型（分别为 10% 或 62%）IP3 受体。因此，肠内分泌细胞的不同亚型以及表达特定激素的个体细胞在调节体内激素释放的分子机制中表现出显着的异质性。这些结果表明，可以开发出可能抑制或促进肠内分泌细胞特定亚型激素分泌的治疗剂。
Enteroendocrine cells are a complex population of intestinal epithelial cells whose hormones play critical roles in regulating gastrointestinal and whole-animal physiology. There are many subpopulations of enteroendocrine cells based on the major hormone(s) produced by individual cells. Intracellular calcium plays a critical role in regulating hormone release. Inositol 1,4,5-trisphophate (IP3) receptors regulate calcium mobilization from endoplasmic reticulum-derived calcium stores in many endocrine and excitatory cells and are expressed in the intestine. However, the specific subtypes of enteroendocrine cells that express these receptors have not been reported. Immunohistochemical (IHC) studies revealed that enteroendocrine cells did not express detectable levels of type 2 IP3 receptors, whereas nearly all enteroendocrine cells that produced chromogranin A and/or serotonin expressed type 1 and type 3 IP3 receptors. Conversely, enteroendocrine cells that produced glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, cholecystokinin, or somatostatin did not express detectable levels of any IP3 receptors. Subsets of enteroendocrine cells that produced substance P or secretin expressed type 1 (33% or 18%, respectively) and type 3 (10% or 62%, respectively) IP3 receptors. Thus, different subtypes of enteroendocrine cells, as well as individual cells that express a particular hormone, exhibit remarkable heterogeneity in the molecular machineries that regulate hormone release in vivo. These results suggest that therapeutic agents can be developed that could potentially inhibit or promote secretion of hormones from specific subtypes of enteroendocrine cells.