Effect of supramaximal cerulein stimulation on mitochondrial energy metabolism in rat pancreas

Hyperstimulation with the cholecystokinin analogue cerulein induces mild edematous pancreatitis in rats. It is believed that an impaired energy metabolism diminishes the cellular defense capacity in the inflamed pancreatic tissue and, therefore, contributes to the injuries in acinar cells. In the present study, changes in the capacity of oxidative phosphorylation were quantified within the first 24 h after subcutaneous cerulein injections. Serum amylase level and pancreatic water content were maximally elevated 5 h after the first injection. The capacity of mitochondrial respiration was reduced in isolated acinar cells to 69 and 44% at 5 and 24 h, respectively, compared to that in saline controls. Simultaneously, glutamate dehydrogenase (GLDH) activity dropped to 70 and 46%. The respiration rates of acinar cells and of isolated mitochondria related to GLDH activities were not different from controls. This suggests that the major portion of the mitochondrial population within the acinar cell is inactivated in the course of cerulein treatment. After 24 h, the reduced population of functionally intact mitochondria restricted the rate of phosphorylating respiration in acinar cells (52%), which resulted in a diminution of cellular ATP to 57%. It is concluded that cerulein hyperstimulation induces a drastic and long-lasting reduction of the capacity for mitochondrial ATP production which may adversely affect energy-requiring reactions of the gland during regeneration.