EFFECT OF SUPRAMAXIMAL CERULEIN STIMULATION ON MITOCHONDRIAL ENERGY-METABOLISM IN RAT PANCREAS

Hyperstimulation with the cholecystokinin analogue cerulein induces mi ld edematous pancreatitis in rats. It is believed that an impaired ene rgy metabolism diminishes the cellular defense capacity in the inflame d pancreatic tissue and, therefore, contributes to the injuries in aci nar cells. In the present study, changes in the capacity of oxidative phosphorylation were quantified within the first 24 h after subcutaneo us cerulein injections. Serum amylase level and pancreatic water conte nt 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 con trols. 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 contro ls. This suggests that the major portion of the mitochondrial populati on within the acinar cell is inactivated in the course of cerulein tre atment, After 24 h, the reduced population of functionally intact mito chondria 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 lon g-lasting reduction of the capacity for mitochondrial ATP production w hich may adversely affect energy-requiring reactions of the gland duri ng regeneration.