Reidelberger Roger D, Hernandez Jessica, Fritzsch Bernd, Hulce Martin
Department of Veterans Affairs-Nebraska Western Iowa Health Care System, and Department of Biomedical Sciences, Creighton University, Omaha, Nebraska, USA.
Am J Physiol Regul Integr Comp Physiol. 2004 Jun;286(6):R1005-12. doi: 10.1152/ajpregu.00646.2003. Epub 2003 Dec 30.
CCK type 1 (CCK1) receptor antagonists differing in blood-brain barrier permeability were used to test the hypothesis that satiety is mediated in part by CCK action at CCK1 receptors on vagal sensory nerves innervating the small intestine. Devazepide penetrates the blood-brain barrier; A-70104, the dicyclohexylammonium salt of N alpha-3-quinolinoyl-D-Glu-N,N-dipentylamide, does not. At dark onset, non-food-deprived control rats and rats with subdiaphragmatic vagotomies received a bolus injection of devazepide (2.5 micromol/kg i.v.) or a 3-h infusion of A-70104 (3 micromol.kg(-1).h(-1) i.v.) either alone or coadministered with a 2-h intragastric infusion of peptone (0.75 or 1 g/h). Food intake was determined from continuous computer recordings of changes in food bowl weight. In control rats both antagonists stimulated food intake and attenuated the anorexic response to intragastric infusion of peptone. In contrast, only devazepide was effective in stimulating food intake in vagotomized rats. Thus endogenous CCK appears to act both at CCK1 receptors beyond the blood-brain barrier and by a CCK1 receptor-mediated mechanism involving abdominal vagal nerves to inhibit food intake.
使用血脑屏障通透性不同的1型胆囊收缩素（CCK1）受体拮抗剂来检验以下假设：饱腹感部分是由CCK作用于支配小肠的迷走感觉神经上的CCK1受体介导的。地伐西匹可穿透血脑屏障；A-70104，即Nα-3-喹啉甲酰-D-谷氨酸-N，N-二戊酰胺的二环己基铵盐，则不能。在黑暗开始时，未禁食的对照大鼠和膈下迷走神经切断的大鼠接受单次静脉注射地伐西匹（2.5微摩尔/千克）或3小时静脉输注A-70104（3微摩尔·千克-1·小时-1），单独使用或与2小时胃内输注蛋白胨（0.75或1克/小时）联合使用。通过连续计算机记录食碗重量变化来确定食物摄入量。在对照大鼠中，两种拮抗剂均刺激食物摄入并减弱对胃内输注蛋白胨的厌食反应。相比之下，只有地伐西匹在迷走神经切断的大鼠中刺激食物摄入有效。因此，内源性CCK似乎既作用于血脑屏障之外的CCK1受体，也通过涉及腹部迷走神经的CCK1受体介导机制来抑制食物摄入。
