Department of Neuroscience, Uppsala University, Sweden.
Acta Physiol (Oxf). 2011 Jan;201(1):141-50. doi: 10.1111/j.1748-1716.2010.02175.x. Epub 2010 Sep 3.
Apelin peptides are the endogenous ligand of the G protein-coupled receptor APJ. Proposed actions include involvement in control of cardiovascular functions, appetite and body metabolism. We have investigated the effects of apelin peptides on duodenal bicarbonate secretion in vivo and the release of cholecystokinin (CCK) from acutely isolated mucosal cells and the neuroendocrine cell line STC-1.
Lewis × Dark Agouti rats had free access to water and, unless fasted overnight, free access to food. A segment of proximal duodenum was cannulated in situ in anaesthetized animals. Mucosal bicarbonate secretion was titrated (pH stat) and apelin was administered to the duodenum by close intra-arterial infusion. Total RNA was extracted from mucosal specimens, reverse transcripted to cDNA and the expression of the APJ receptor measured by quantitative real-time PCR. Apelin-induced release of CCK was measured using (1) cells prepared from proximal small intestine and (2) STC-1 cells.
Even the lowest dose of apelin-13 (6 pmol kg⁻¹ h⁻¹) caused a significant rise in bicarbonate secretion. Stimulation occurred only in continuously fed animals and even a 100-fold greater dose (600 pmol kg⁻¹ h⁻¹) of apelin was without effect in overnight food-deprived animals. Fasting also induced an eightfold decrease in the expression of APJ receptor mRNA. Apelin induced significant release of CCK from both mucosal and STC-1 cells, and the CCK(A) receptor antagonist devazepide abolished bicarbonate secretory responses to apelin.
Apelin-induced stimulation of duodenal electrolyte secretion is feeding-dependent and mediated by local mucosal release of CCK.
Apelin 肽是 G 蛋白偶联受体 APJ 的内源性配体。其作用包括参与心血管功能、食欲和身体代谢的控制。我们研究了 Apelin 肽对体内十二指肠碳酸氢盐分泌的影响，以及从急性分离的黏膜细胞和神经内分泌细胞系 STC-1 释放胆囊收缩素（CCK）的情况。
Lewis×Dark Agouti 大鼠可以自由饮水，除非隔夜禁食，否则可以自由进食。在麻醉动物中，原位对近端十二指肠段进行插管。通过近距离动脉内输注向十二指肠给药，滴定黏膜碳酸氢盐分泌（pH -stat）。从黏膜标本中提取总 RNA，反转录为 cDNA，并通过定量实时 PCR 测量 APJ 受体的表达。通过（1）从小肠近端制备的细胞和（2）STC-1 细胞测量 Apelin 诱导的 CCK 释放。
即使是最低剂量的 Apelin-13（6 pmol kg⁻¹ h⁻¹）也能显著增加碳酸氢盐分泌。刺激仅发生在持续进食的动物中，即使是禁食过夜动物中 100 倍更高剂量（600 pmol kg⁻¹ h⁻¹）的 Apelin 也没有作用。禁食还导致 APJ 受体 mRNA 的表达降低了 8 倍。Apelin 诱导黏膜和 STC-1 细胞中 CCK 的显著释放，而 CCK(A)受体拮抗剂 devazepide 消除了 Apelin 对碳酸氢盐分泌反应。
Apelin 诱导的十二指肠电解质分泌刺激是进食依赖性的，由局部黏膜释放 CCK 介导。
