Time-specific development of pancreatic hypersecretory capacity during chronic caerulein treatment in rats

It is well established that repeated injections of the cholecystokinin (CCK) analogue caerulein induce pancreatic hypersecretion and growth, but so far the time-specific development of hypersecretory capacity has not been studied. Rats were given intraperitoneal injections of caerulein (1 microgram/kg) three times daily for 0-7 days. On the day after the last injection a secretory test was performed with the rats under urethane anaesthesia. Subsequently, pancreatic tissue composition was analysed. Basal and caerulein-stimulated secretion rates of fluid and trypsin were elevated after as little as 1 day of caerulein treatment. These values remained significantly greater than those of the controls after 2-7 days' administration of the peptide. Pancreatic tissue hypertrophy (increases in absolute pancreatic weight, protein and trypsin contents, and also in these values normalized to DNA) appeared after 2 days' pretreatment. Tissue growth turned to hyperplasia (increase in tissue DNA content) after 5 days' caerulein administration. We conclude that chronic administration of the CCK analogue caerulein induces adaptation of the pancreas in a sequential order. First, the hypersecretory state appears, followed by hypertrophy, and, finally, pancreatic growth turns into hyperplasia.