Chi Michael M, Powley Terry L
Dept. of Psychological Sciences, Purdue Univ., 703 Third St., West Lafayette, IN 47907-2004, USA.
Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R1170-83. doi: 10.1152/ajpregu.00015.2003. Epub 2003 Jun 19.
The mouse W/Wv mutation of the c-Kit receptor causes extensive loss of gastrointestinal interstitial cells of Cajal and vagal intramuscular arrays (IMAs; one of the two putative mechanoreceptors in gastrointestinal smooth muscle). To characterize the behavioral phenotype of the c-Kit mouse and to evaluate the roles of these mechanoreceptors in controlling food intake, meal patterns and daily intakes of W/Wv mice and controls were examined using solid (20-mg pellets) and liquid (Isocal) maintenance diets. After the meal pattern experiments, CCK (0.5, 1, 2, 4, 8, and 16 microg/kg ip) was administered to examine the role of the interstitial cells and vagal IMA mechanoreceptors in relaying peripheral signals of satiety activated by CCK-A receptors, whereas the specificity of the response was assessed with the antagonist devazepide (300 microg/kg ip). On both diets, the W/Wv mice ate smaller meals for shorter durations, with a compensatory increase in meal number, resulting in daily intakes and body weights similar to the controls. After CCK injections, the mutant mice consistently suppressed intake more ( approximately 2x) in 30-min tests, regardless of the test diet (12.5% glucose, chow, pellets, and Isocal). The increased sensitivity of W/Wv mice to CCK reflected an increased potency of the hormone (c-Kit mouse ED50 = 2.4 microg/kg; control ED50 = 6.4 microg/kg) and a shift of the dose-response curve to the left. Devazepide blocked the CCK suppression of ingestion. These results indicate that the selective loss of the interstitial cells and IMAs disrupts short-term feeding of the W/Wv mice by inducing an earlier satiety, possibly by altering gastric accommodation and/or emptying, without affecting the long-term mechanisms controlling overall intake or body weight. The results also suggest that the reduction of interstitial cells and IMAs augments the sensitivity to or increases the efficiency of exogenous CCK.
c-Kit受体的小鼠W/Wv突变导致胃肠道Cajal间质细胞和迷走神经肌内排列（IMA；胃肠道平滑肌中两种假定的机械感受器之一）大量缺失。为了表征c-Kit小鼠的行为表型并评估这些机械感受器在控制食物摄入、进餐模式和每日摄入量方面的作用，使用固体（20毫克颗粒）和液体（等热量饮料）维持饮食对W/Wv小鼠和对照小鼠进行了检查。在进餐模式实验后，给予CCK（0.5、1、2、4、8和16微克/千克腹腔注射）以研究间质细胞和迷走神经IMA机械感受器在传递由CCK-A受体激活的饱腹感外周信号中的作用，而使用拮抗剂地伐西匹（300微克/千克腹腔注射）评估反应的特异性。在两种饮食条件下，W/Wv小鼠每餐进食量较小，进食时间较短，进餐次数有代偿性增加，导致每日摄入量和体重与对照小鼠相似。注射CCK后，在30分钟测试中，突变小鼠无论测试饮食（12.5%葡萄糖、食物、颗粒和等热量饮料）如何，始终更多地抑制摄入量（约2倍）。W/Wv小鼠对CCK的敏感性增加反映了该激素效力的增加（c-Kit小鼠ED50 = 2.4微克/千克；对照ED50 = 6.4微克/千克）以及剂量反应曲线向左移动。地伐西匹阻断了CCK对摄食的抑制作用。这些结果表明，间质细胞和IMA的选择性缺失通过诱导更早的饱腹感破坏了W/Wv小鼠的短期进食，可能是通过改变胃容纳和/或排空，而不影响控制总体摄入量或体重的长期机制。结果还表明，间质细胞和IMA的减少增强了对外源性CCK的敏感性或提高了其效率。
