[Applicability of CCK receptor antagonists in physiologic and therapeutic studies]

The development of potent and specific CCK-receptor antagonists made it possible to evaluate the physiological role of CCK for various gastrointestinal functions. The results of these studies show that CCK is the hormone which principally mediates meal-induced gallbladder emptying. In addition, CCK appears to play an important role in maintaining the fasting muscular tone of the gallbladder. In contrast, CCK-antagonists could inhibit only about 50% of the meal-stimulated pancreatic exocrine secretion. Because of their marked relaxing effect on the gallbladder, CCK-antagonists might become an important clinical tool for treatment of gallbladder spasms and colics. On the other hand, long-term application of CCK-antagonists will increase the risk of stone formation in the gallbladder. CCK-antagonists also had beneficial effects in some animal models of acute pancreatitis. As yet, it is unclear whether CCK-antagonists might become useful for the treatment of human pancreatitis. Since CCK-antagonists only slightly inhibited pancreatic growth, it is unlikely that they will exert major inhibitory effects against growth of pancreatic carcinoma. CCK-antagonists failed to alter gastric emptying of a normal mixed solid-liquid meal, but accelerated gastric emptying of purely liquid meals. Thus, CCK-antagonists are not likely to become useful agents to treat alterations of gastric emptying. The studies with CCK-antagonists further showed that CCK plays only a minor role in the regulation of the motility of the small and large intestine. CCK is probably not involved in the regulation of the gastrocolonic response after a meal. Some reports indicate that CCK-antagonists might increase colonic transit and might therefore be useful to treat constipation.