CCK ADMINISTRATION AFTER CCK RECEPTOR BLOCKADE ACCELERATES RECOVERY FROM CERULEIN-INDUCED ACUTE-PANCREATITIS IN RATS

We examined the effects of treatment with cholecystokinin (CCK) octape ptide (CCK-8) and the CCK receptor antagonist loxiglumide on the recov ery of exocrine pancreas in post-acute pancreatitic rats. Acute pancre atitis was induced in rats by intravenous infusion of 20 mu g/kg/h cer ulein for 4 h. At 24 h after the start of cerulein infusion, rats were divided into nine treatment groups: oral administration of saline (co ntrol), or oral administration of 10 or 50 mg/kg body weight loxiglumi de twice daily for the first 3 days, followed by saline administration (Loxi-1 and Loxi-2), 10 or 50 mg/kg body weight loxiglumide twice dai ly for 6 days (Loxi-3 and Loxi-4), oral administration of saline or 10 or 50 mg/kg body weight loxiglumide twice daily for the first 3 days, followed by subcutaneous injection of 2.5 mu g/kg body weight CCK-8 t wice daily for the next 3 days (CCK-1, CCK-2, and CCK-3), and subcutan eous injection of 2.5 mu g/kg body weight CCK-8 twice daily for 6 days (CCK-4). Pancreatic wet weight and biochemical changes were evaluated on day 8 at 12 h after the last treatment. Treatment with loxiglumide (Loxi-3 and Loxi-4) or CCK-8 for 6 days (CCK-4) or with a high dose o f loxiglumide for the first 3 days (Loxi-2) significantly suppressed t he recovery of pancreatic weight and DNA content compared to saline tr eatment or to the untreated normal control rats. However, when loxiglu mide treatment was followed by 3 days of CCK-8 injections (CCK-2 and C CK-3), pancreatic protein and DNA content recovered to levels comparab le to or above the control levels. The most remarkable increase in enz yme content was obtained in postpancreatitic rats treated with high-do se loxiglumide for the first 3 days, followed by CCK-8 injection (CCK- 3). On the other hand, 6 days of CCK-8 treatment (CCK-4) had no signif icant influences on pancreatic enzyme contents. These results suggest that the most favorable strategy for the treatment of acute pancreatit is is to give high-dose loxiglumide during the early stage for only a short period, followed by CCK-8 administration.