The chronically reserpinized rat as a possible model for cystic fibrosis. VII. Alterations in the secretory response to cholecystokinin and to secretin from the pancreas in vivo.

The chronically reserpinized rat has been proposed as an animal model for 
cystic fibrosis on the basis of morphologic and secretory alterations in 
the submaxillary gland and of abnormalities in pulmonary secretions. In this 
investigation, the volume and composition of pancreatic juice from reserpine treated 
rats (0.5 mg/kg/day) have been compared to those of untreated controls 
after stimulation with purified cholecystokinin (0.1 microgram/kg body weight) and with 
crude and purified preparations of secretin (6 microns/100 g body weight) 
infused iv for 30-min periods. The results demonstrate that the treated 
animals secreted a significantly lower volume of pancreatic juice after stimulation 
with these secretagogues. Flow rates were also significantly reduced after stimulation 
with cholecystokinin and crude secretin. Protein and amylase outputs in response 
to cholecystokinin were smaller than in control animals after unrestritced feedings, 
but greater after a 24-hr fast. Total bicarbonate output was also 
reduced after stimulation with either crude or purified secretin and the 
normal excretion patterns for bicarbonate and chloride were either absent of 
reversed in the secretin-stimulated pancreatic juice of the treated animals. Whole 
pancreas homogenates from the treated animals showed significant increases in Ca++ 
and protein content. These results indicate that chronic administration of reserpine 
alters the secretion of water, protein, and bicarbonate from the rat 
pancreas and that it affects several of the exocrine glands involved 
in cystic fibrosis. These findings lend support to the concept of 
an animal model for the human disease. The chronic administration of 
reserpine to rats has been shown to induce alterations in salivary 
and pulmonary secretions which resemble those seen in patients with cystic 
fibrosis. The concept of an animal model has been proposed on 
the basis of these observations. The pancreas is another exocrine gland 
prominently involved in cystic fibrosis and if it can be demonstrated 
that reserpine administration also induces alterations in pancreatic secretion, the concept 
of the animal model would be strengthened considerably. 