ENERGY-METABOLISM IN MOUSE PANCREAS IN RESPONSE TO DIFFERENT DOSAGES OF A CCK ANALOG

Stimulation of the exocrine pancreas with cholecystokinin analogues le ads to a variety of intraacinar processes, many coupled to energy cons umption. It was hypothesized that extensive ATP depletion could play a role in the pathophysiology of acute pancreatitis, especially in the hyperstimulation (cerulein) model. Mice received seven intraperitoneal injections of cerulein at hourly intervals, at doses ranging from phy siological (0.1 mu g/kg) to pharmacological (50 mu g/kg). A single dos e of cerulein induced a 28-33% decrease in ATP, whereas a complete cou rse of injections led to a nadir as low as 45% of the control value. T he overall pattern of ATP tissue content during the observed time cour se was surprisingly similar in all four groups and statistically not d ifferent at any time point. Until 12 h, ATP levels in all groups remai ned below the control value. In contrast, serum amylase and light micr oscopy reflected a degree of pancreatitis in a close dose-response pat tern to the administered cerulein dose. These findings suggest that AT P depletion-although probably facilitating acinar damage-does not seem to play a causal or primary role in the pathophysiology of acute panc reatitis.