Exocrine Pancreatic Secretion in Anesthetized Rats

The effect of a candidate compound on pancreas secretion can be measured in rats with acute pancreas fistula. For safety pharmacological assessment of candidate compounds the decrease of exocrine pancreatic secretion might be problematic due to the potential of induction of pancreatitis. 

Rats weighing 150-200 g are used. Eighteen hours prior to the experiment food is withdrawn with free access to water. The appropriate size of the study groups for the control and candidate compound consists of 5-7 animals. Anesthesia is induced by pentobarbital (priming bolus 60 mg/kg i.p. plus infusion s.c. at about 20 mg/kg/h) or i.p. injection of 5 ml/kg of 25 % urethane solution. Body temperature is artificially stabilized by means of a rectal thermometer and a heating pad. The trachea is exposed and cannulated for artificial respiration. The abdomen is opened by a mid-line incision and the pylorus ligated. The proximal part of the bile duct is ligated near the hepatic 

The secretion after injection of the test compound is compared with the pre-test values. Secretin or cholecystokinin (CCK) increases pancreatic secretion volume in a dose-dependent manner and can be used as a positive standard. 

Guan et al. (1990) inserted two separate cannulas for bile and pancreatic juice to rats under methoxyfluorane anesthesia. Both fluids were returned to the intestine. Placing the rats in modified Bollman-type restraint cages, experiments could be performed after a few days in conscious animals. 

Ito et al. (1994) studied the inhibition of CCK-8-induced pancreatic amylase secretion by a cholecystokinin type-A receptor antagonist in rats. 

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Pedersen, N.L.-R., Nagain-Domaine, C., Mahe, S., Chariot, J., Roze, C., and Tome, D. 2000. Caseinomacropeptide specifically stimulates exocrine pancreatic secretion in anesthetized rat. Peptides 21, 1527-1535. 

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