Effects of peripheral CCK receptor blockade on feeding responses to duodenal nutrient infusions in rats
Effects of peripheral CCK receptor blockade on feeding responses to duodenal nutrient infusions in rats
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DOI：
10.1152/ajpregu.00529.2002
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发表时间：
2003-02-01
影响因子：
2.8
通讯作者：
Hulce, M
中科院分区：
文献类型：
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作者：
Reidelberger, RD;Heimann, D;Hulce, M
A型胆囊收缩素受体（CCKAR）拮抗剂在血脑屏障渗透性不同，用于测试的假设，十二指肠蛋白质，碳水化合物和脂肪的输送产生饱腹感的一部分，通过一个必不可少的CCK行动在位于外周血脑屏障的CCKAR。空腹大鼠开放性胃瘘接受devazepide（1 mg/kg iv）或A-70104（700 nmol.kg（-1）.h（-1）iv），并在30分钟内静脉输注CCK-8（10 nmol.kg（-1）.h（-1））或十二指肠输注蛋白胨、麦芽糖或Intraperoid，开始时间为10分钟，然后30分钟进入15%蔗糖。Devazepide可穿透血脑屏障; A-70104（N α-3-喹啉酰基- D-Glu- N，N-二戊基酰胺的二环己基铵盐）则不能。CCK-8对假喂食的抑制率接近50%，A-70104和devazepide都能消除这种反应。十二指肠输注每种常量营养素剂量依赖性地抑制假喂养。A-70104和devazepide减弱了对每种常量营养素的抑制反应。因此，内源性CCK似乎部分作用于血脑屏障周围的CCKAR，以抑制食物摄入。
Type A cholecystokinin receptor (CCKAR) antagonists differing in blood-brain barrier permeability were used to test the hypothesis that duodenal delivery of protein, carbohydrate, and fat produces satiety in part by an essential CCK action at CCKARs located peripheral to the blood-brain barrier. Fasted rats with open gastric fistulas received devazepide (1 mg/kg iv) or A-70104 (700 nmol.kg(-1).h(-1) iv) and either a 30-min intravenous infusion of CCK-8 (10 nmol.kg(-1).h(-1)) or duodenal infusion of peptone, maltose, or Intralipid beginning 10 min before 30-min access to 15% sucrose. Devazepide penetrates the blood-brain barrier; A-70104, the dicyclohexylammonium salt of Nalpha-3-quinolinoyl- D-Glu- N,N-dipentylamide, does not. CCK-8 inhibited sham feeding by similar to50%, and both A-70104 and devazepide abolished this response. Duodenal infusion of each of the macronutrients dose dependently inhibited sham feeding. A-70104 and devazepide attenuated inhibitory responses to each macronutrient. Thus endogenous CCK appears to act in part at CCKARs peripheral to the blood-brain barrier to inhibit food intake.