Sievert C E, Potter T J, Levine A S, Morley J E, Silvis S E, Vennes J A
Gastroenterology Department, Veterans Administration Medical Center, Minneapolis, Minnesota 55417.
Am J Physiol. 1988 Mar;254(3 Pt 1):G361-5. doi: 10.1152/ajpgi.1988.254.3.G361.
This study reports the effects of bombesin and gastrin-releasing peptide (GRP) on the canine sphincter of Oddi using a method that allows repeated cannulation of the biliary sphincter in the unanesthetized animal through a Thomas cannula placed opposite the biliary papilla. Immediately after intravenous administration of bombesin or GRP, phasic sphincter contractions disappeared, basal sphincter pressures fell, and common bile duct pressures rose. Because bombesin releases cholecystokinin (CCK) and CCK resulted in a similar pattern to that of bombesin, the bombesin effect on the sphincter of Oddi may have been secondary to CCK's effect on the sphincter. To test if the bombesin effect on the sphincter of Oddi was due to the release of CCK, we blocked CCK release by administration of somatostatin, having first established that somatostatin blocked endogenous CCK release in our animal model by use of an intraduodenal infusion of lipid. Exogenous administration of bombesin failed to alter sphincter of Oddi or common bile duct pressures in dogs treated with somatostatin. Somatostatin did not, however, block CCK's effect on gallbladder contraction, since exogenous administration of CCK after somatostatin injection resulted in the pressure changes in the biliary tree typical of CCK-induced gallbladder contraction. Thus bombesin administration appears to result in sphincter relaxation and gallbladder contraction by the release of endogenous CCK rather than by a direct effect. The increase in common bile duct pressures was due to gallbladder contraction, since this rise in pressure was abolished by cholecystectomy. The peptide effect on sphincter contraction and basal sphincter pressure were unaffected by cholecystectomy.
本研究报告了蛙皮素和胃泌素释放肽（GRP）对犬奥迪括约肌的影响，所采用的方法能够通过放置在胆管乳头对面的托马斯套管，在未麻醉的动物身上对胆管括约肌进行重复插管。静脉注射蛙皮素或GRP后，括约肌的阶段性收缩立即消失，括约肌基础压力下降，胆总管压力升高。由于蛙皮素可释放胆囊收缩素（CCK），且CCK产生的作用模式与蛙皮素相似，因此蛙皮素对奥迪括约肌的作用可能继发于CCK对该括约肌的作用。为了检验蛙皮素对奥迪括约肌的作用是否归因于CCK的释放，我们通过注射生长抑素阻断CCK的释放，在此之前我们已利用十二指肠内输注脂质的方法确定生长抑素在我们的动物模型中可阻断内源性CCK的释放。对接受生长抑素治疗的犬，外源性给予蛙皮素未能改变奥迪括约肌或胆总管压力。然而，生长抑素并未阻断CCK对胆囊收缩的作用，因为在注射生长抑素后外源性给予CCK会导致胆管树出现CCK诱导的胆囊收缩典型的压力变化。因此，给予蛙皮素似乎是通过释放内源性CCK而非直接作用导致括约肌松弛和胆囊收缩。胆总管压力升高是由于胆囊收缩，因为胆囊切除术后这种压力升高消失。胆囊切除术不影响肽对括约肌收缩和括约肌基础压力的作用。
