Role of cholecystokinin in the development and progression of acute pancreatitis and the potential of therapeutic application of cholecystokinin receptor antagonists

There is also evidence that CCK antagonists have a potential therapeutic be nefit. Clinical studies will evaluate their therapeutic potential for patie nts with AP. This presentation reviews the role of cholecystokinin (CCK) as a contributory factor for the development and progression of acute pancrea titis (AP) and the perspective of CCK receptor antagonists for treatment of AP. High, supraphysiological concentrations of CCK induce AP in various sp ecies including man. There is also evidence that physiological increases in plasma CCK deteriorates AP in several animal models. The latter findings s upport the hypothesis that CCK plays a contributory or permissive role for the development of AP. The majorities of experimental studies show that the prophylactic and therapeutic use of CCK antagonists ameliorates AP. The la tter effects were clearly shown for models of biliary AP in which plasma CC K is increased due to a feedback mechanism. However, CCK antagonists also h ad beneficial effects in models in which plasma CCK is; not increased. In a nimal strains which do not have a CCK-A-receptor due to a genetic abnormali ty AP induced by a certain noxious factor does not develop to the same seve rity when compared to animals with a normal CCKA-receptor. Thus, CCK acts a s a permissive or contributory factor for the development and progression o f AP. There is also evidence that CCK antagonists have a potential therapeu tic benefit. Clinical studies will evaluate their therapeutic potential for patients with AP.