devazepide and Cholestasis

The aim of this study was to examine the effect of the most potent CCK receptor antagonist, L364,718, on two major factors involved in pancreatitis development: enzyme load and cytosolic calcium (Ca2+) levels in acinar cells. L364,718 (0.1 mg/kg/12 hr) was administered from 30 min before inducing acute pancreatitis (AP) by pancreatic duct obstruction (PDO) for 48 hr. The results obtained at different AP stages in PDO rats treated and not treated with the CCK antagonist were compared. Similar increases in the intracellular enzyme content were found at earlier stages of pancreatitis in all PDO rats treated or not treated with L364,718. The CCK antagonist increased cytosolic Ca2+ levels up to 6 hr after administration, inducing a higher cytosolic Ca2+ overload at the earliest stages of pancreatitis in L364,718-treated PDO rats than in those not treated. This event might justify the higher increases in ascites volume and haematocrit found in PDO rats treated with L364,718 and the exacerbation in pancreatic morphological alterations induced by PDO. The CCK receptor antagonist L364,718 produces alterations in the acinar calcium homeostasis that prevent to reduction in the severity of pancreatitis induced by obstruction.

Topics: Acute Disease; Amylases; Animals; Calcium; Cholecystokinin; Cholestasis; Devazepide; Hormone Antagonists; Male; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Wistar; Trypsinogen

We conducted a study to examine the role of cholecystokinin in feeding behavior and weight change in rats with obstructive jaundice. Daily food and water intake, body weight, and short-term food intake were determined in two groups of rats with surgically induced obstructive jaundice and in control rats. One group of rats with obstructive jaundice was given L-364,718, a selective cholecystokinin receptor antagonist. Plasma bilirubin and cholecystokinin levels were measured in each rat before and 7 days after surgery. Daily food intake and body weight were decreased in obstructive jaundice rats compared with control rats during the first week after surgery (P less than .05); however, obstructive jaundice rats treated with L-364,718 had increased food intake and body weight (P less than .05). Short-term food intake measured for 30 minutes and 120 minutes in food-deprived obstructive jaundice rats was decreased when compared with control rats (P less than .05), but the obstructive jaundice rats given L-364,718 had increased short-term food intake (P less than .05). Water intake was similar between the two groups of rats. Plasma levels of cholecystokinin and bilirubin were increased in obstructive jaundice rats with and without L-364,718 treatment (P less than .05). The results support the concept that endogenously elevated levels of plasma cholecystokinin play an important role in decreased food intake and subsequent loss of body weight in rats with obstructive jaundice.

Topics: Animals; Benzodiazepinones; Bilirubin; Body Weight; Cholecystokinin; Cholestasis; Devazepide; Feeding Behavior; Male; Rats; Rats, Inbred Strains