Einfluss unterschiedlicher Cholezystokinin-Analoga auf die Amylasesekretion isolierter Rattenpankreas-Azini

Abstract

Experimental models of secretory hyperstimulation are used frequently to study the pathophysiology of acute pancreatitis. The cholecystokinin (CCK) analogue ceruletide (Takus®) which is also applied in human medicine is one of the most popular secretagogues. Takus® contains thiomalate (mercaptosuccinat) as a preservative. Thiomalate is known as an inhibitor of the antioxidant enzyme glutathione peroxidase. We tested the hypothesis that the results of secretory stimulation of the pancreas by Takus® may be influenced by the preservative. Acini were isolated from rat pancreas and exposed to the secretagogues ceruletide (Takus®), ceruletide free of preservative (lyophilised Takus®), or cholecystokinin octapeptide (CCK-8) as well as to the preservative alone. Amylase secretion by the acini was measured after 30 min and 60 min of exposure to different concentrations of the secretagogues (10^-6 M - 10^-11 M). All three secretagogues stimulated amylase secretion in a concentration-dependent manner with a submaximal (10^-11 M), an optimal (10^-10 M) and an inhibitory (10^-9 M - 10^-6 M) range. At optimally stimulating concentration, lyophilised Takus® was the most powerful secretagogue followed by CCK-8 and Takus®. Thiomalate at 8 nM - 8 mM was a weak, but at > 80 mM a powerful inhibitor of amylase secretion. Thus, lyophilised Takus® or CCK-8 should be preferentially used vs. Takus® in studies investigating pancreatic secretion. The results may also have relevance to animal models that use supraphysiologic doses of Takus® to induce mild acute pancreatitis since Takus® may provoke oxidative stress independent of pancreatitis itself via inhibition of the antioxidant enzyme glutathione oxidase by the preservative thiomalate. However, this latter suggestion has to be proven by a subsequent investigation.