Thimister P W, Hopman W P, Sloots C E, Rosenbusch G, Tangerman A, Willems H L, Lamers C B, Jansen J B
Department of Gastroenterology, University Hospital, Nijmegen, The Netherlands.
Gastroenterology. 1994 Dec;107(6):1627-35. doi: 10.1016/0016-5085(94)90801-x.
BACKGROUND/AIMS: Bombesin-stimulated plasma cholecystokinin levels decrease after an initial increase despite continuous infusion of bombesin. The aim of this study was to determine if a feedback mechanism, mediated by bile salts or proteolytic enzymes, is responsible for this decline.
Bombesin (1.0 ng.kg-1.min-1) was infused into volunteers for 180 minutes on separate occasions. Cholestyramine, colestipol, camostate, or saline were perfused intraduodenally during the second hour of the tests. Cholestyramine was also administered without infusion of bombesin.
Colestipol and cholestyramine, dependent on their bile salt-binding capacity, markedly enhanced (P < 0.05) bombesin-stimulated plasma cholecystokinin from 2.1 +/- 0.5 pmol/L to 6.4 +/- 2.2 pmol/L and 12.1 +/- 3.3 pmol/L (P < 0.05 vs. colestipol), respectively, and further decreased gallbladder volume (P < 0.05) from 9.4 +/- 1.6 mL to 2.0 +/- 0.4 mL and 2.2 +/- 0.5 mL, respectively. The protease inhibitor camostate had no effect. Bile salt precipitation also enhanced plasma pancreatic polypeptide responses (P < 0.01) but did not alter gastrin responses. Plasma cholecystokinin responses to cholestyramine without bombesin infusion varied considerably, but increments were highly correlated to decreases in gallbladder volume (r = 0.91; P < 0.005).
Bile salt sequestration but not protease inactivation enhances plasma cholecystokinin and gallbladder responses to bombesin infusion in humans.
背景/目的：尽管持续输注蛙皮素，但蛙皮素刺激后的血浆胆囊收缩素水平在最初升高后会下降。本研究的目的是确定由胆盐或蛋白水解酶介导的反馈机制是否是导致这种下降的原因。
在不同时间向志愿者输注蛙皮素（1.0 ng·kg-1·min-1），持续180分钟。在试验的第二个小时期间，将考来烯胺、考来替泊、抑肽酶或生理盐水经十二指肠灌注。考来烯胺也在未输注蛙皮素的情况下给药。
考来替泊和考来烯胺根据其胆盐结合能力，分别将蛙皮素刺激后的血浆胆囊收缩素从2.1±0.5 pmol/L显著提高至6.4±2.2 pmol/L和12.1±3.3 pmol/L（与考来替泊相比，P<0.05），并使胆囊体积分别从9.4±1.6 mL进一步减小至2.0±0.4 mL和2.2±0.5 mL（P<0.05）。蛋白酶抑制剂抑肽酶没有效果。胆盐沉淀也增强了血浆胰多肽反应（P<0.01），但未改变胃泌素反应。在未输注蛙皮素的情况下，血浆胆囊收缩素对考来烯胺的反应差异很大，但增量与胆囊体积的减小高度相关（r=0.91；P<0.005）。
胆盐螯合而非蛋白酶失活增强了人体血浆胆囊收缩素和胆囊对蛙皮素输注的反应。
