Kreiss C, Schwizer W, Borovicka J, Jansen J B, Bouloux C, Pignol R, Bischof Delaloye A, Fried M
Department of Gastroenterology, University Hospital, Lausanne, Switzerland.
Regul Pept. 1998 Jun 30;74(2-3):143-9. doi: 10.1016/s0167-0115(98)00035-4.
The role of cholecystokinin (CCK) in the regulation of gastric emptying of physiological meals containing solids and liquids in humans remains controversial. We studied the role of endogenous CCK in the emptying of a solid/liquid meal administering the new, highly specific and potent CCK-A receptor antagonist lintitript. Gastric emptying was assessed in nine healthy male volunteers using a randomized, double blind, two-period crossover design with oral lintitript (15 mg 1 h prior to meal intake) or placebo on two different days. After ingestion of a pancake (570 kcal) labelled with 500 microCi of 99mTc-sulfur colloid and 500 ml 10% dextrose containing 80 microCi. 111In-DTPA, subjects were studied in a sitting position, using a dual-headed gamma camera. Plasma CCK and pancreatic polypeptide (PP) were measured by a specific RIA. Lintitript distinctly accelerated gastric emptying of solids, while gastric emptying of liquids was not significantly altered. The lag period was shortened by 20% (P<0.05), AUC and half emptying time of solid emptying were lowered by 12% and 13%, respectively (P<0.03). Lintitript markedly increased postprandial plasma CCK release (P<0.001) while distinctly reducing postprandial PP levels (P<0.01) as compared to placebo. These data provide further evidence for a significant role of CCK in the regulation of gastric emptying of solids. The study demonstrates for the first time the marked gastrokinetic properties of the new CCK-A receptor antagonist lintitript in humans.
胆囊收缩素（CCK）在调节人体含固体和液体的生理性餐食胃排空过程中的作用仍存在争议。我们通过给予新型、高度特异性且强效的CCK - A受体拮抗剂林替曲普，研究内源性CCK在固体/液体餐食排空中的作用。采用随机、双盲、两期交叉设计，在9名健康男性志愿者中评估胃排空情况，在两个不同日期分别口服林替曲普（进餐前1小时服用15毫克）或安慰剂。在摄入标有500微居里99mTc - 硫胶体的煎饼（570千卡）和含有80微居里111In - DTPA的500毫升10%葡萄糖后，让受试者坐在位置上，使用双头γ相机进行研究。通过特异性放射免疫分析法测定血浆CCK和胰多肽（PP）。林替曲普明显加速了固体的胃排空，而液体的胃排空没有显著改变。延迟期缩短了20%（P<0.05），固体排空的曲线下面积（AUC）和半排空时间分别降低了12%和13%（P<0.03）。与安慰剂相比，林替曲普显著增加了餐后血浆CCK释放（P<0.001），同时明显降低了餐后PP水平（P<0.01）。这些数据进一步证明了CCK在调节固体胃排空方面的重要作用。该研究首次证明了新型CCK - A受体拮抗剂林替曲普在人体中具有显著的胃动力特性。
