CCK administration after CCK receptor blockade accelerates recovery from cerulein-induced acute pancreatitis in rats.
We examined the effects of treatment with cholecystokinin (CCK) octapeptide (CCK-8) and the CCK receptor antagonist loxiglumide on the recovery of exocrine pancreas in post-acute pancreatitic rats. Acute pancreatitis was induced in rats by intravenous infusion of 20 microg/kg/h cerulein for 4 h. At 24 h after the start of cerulein infusion, rats were divided into nine treatment groups: oral administration of saline (control), or oral administration of 10 or 50 mg/kg body weight loxiglumide 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 daily 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 microg/kg body weight CCK-8 twice daily for the next 3 days (CCK-1, CCK-2, and CCK-3), and subcutaneous injection of 2.5 microg/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 of loxiglumide for the first 3 days (Loxi-2) significantly suppressed the recovery of pancreatic weight and DNA content compared to saline treatment or to the untreated normal control rats. However, when loxiglumide treatment was followed by 3 days of CCK-8 injections (CCK-2 and CCK-3), pancreatic protein and DNA content recovered to levels comparable to or above the control levels. The most remarkable increase in enzyme content was obtained in postpancreatitic rats treated with high-dose 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 significant influences on pancreatic enzyme contents. These results suggest that the most favorable strategy for the treatment of acute pancreatitis is to give high-dose loxiglumide during the early stage for only a short period, followed by CCK-8 administration.
Nakano
S
S
Third Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Kihara
Y
Y
Otsuki
M
M
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002108:Ceruletide; D002766:Cholecystokinin / Q000008:administration & dosage / Q000627:therapeutic use*; D004247:DNA / Q000378:metabolism; D006727:Hormone Antagonists / Q000627:therapeutic use*; D008049:Lipase / Q000378:metabolism; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011377:Proglumide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D012038:Regeneration; D012844:Sincalide / Q000627:therapeutic use; D014357:Trypsin / Q000378:metabolism
D006727:Hormone Antagonists; D011949:Receptors, Cholecystokinin; C053737:loxiglumide; D002108:Ceruletide; D004247:DNA; D002766:Cholecystokinin; D008049:Lipase; D000681:Amylases; D014357:Trypsin; D011377:Proglumide; D012844:Sincalide