Time-course of the pancreatic changes following long-term stimulation or inhibition of the CCK-A receptor

Cholecystokinin (CCK) reportedly induces both hyperplastic and hypertrophic changes in the pancreas. Blockade of the CCK receptor results in decreased pancreatic secretion and atrophy. The aim of this study was to evaluate the time-course of the effects of stimulation and inhibition of the CCK-A receptor in the rat exocrine pancreas. Male rats had infusion of sulfated CCK-8, the CCK-A receptor antagonist devazepide, or sodium chloride by osmotic minipumps. After 36 h, 3, 7, or 28 d the rats had ip injections of thymidine, and 1 h later they were sacrificed. The pancreas was excised, weighed, and its content of protein, DNA, water, and enzymes was analyzed. Histologic samples were prepared for autoradiography. Pancreatic weight, protein, and DNA were increased at 36 h after the start of CCK infusion and throughout the study period. CCK stimulation also increased the content of trypsin at days 3 and 28. The labeling index of pancreatic acinar cells was increased at 36 h. Blockade of endogenous CCK by the receptor antagonist devazepide led to decreased pancreatic weight from the third day of infusion, whereas the protein content was decreased from the seventh day. At day 28, the DNA content was decreased by devazepide. However, the labeling index of acinar cells decreased transiently already at 36 h. Neither CCK nor devazepide caused any changes of protein content:DNA content ratio during the study. Continuous infusion of CCK caused pancreatic hyperplasia already after 36 h. Stimulation up to 28 d did not cause any further effects. The adverse changes found after blockade of the CCK-A receptor showed much of the same time-course.