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

Abstract

Summary .isoproterenol (8). In the second model, we have demonstratedThe 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 pg/ kg body wt) and with crude and purified preparations of secretin (6p/100 g body wt) 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. Fldw rates were also significantly reduced after stimulation with cholecvstokinin and crude secretin. Protein and amylase outputs in response to cholecystokinin were smaller than in control animals after unrestricted 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 or 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. SpeculationThe 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.The generalized exocrine gland dysfunction which is characteristic of cystic fibrosis (3) has been partially reproduced in experimental animal models induced by treating rats in a chronic fashion with certain drugs that influence the level of autonomic input into these tissues. In the first of these models, changes in the excretion of monovalent ions and of basic proteins from the rat parotid gland were observed after chronic administration of that administration of reserpine for several days induces morphologic and secretory changes in the rat submaxillary gland which resemble those of cystic fibrosis (CF) (11,12). In addition, we have shown that this procedure increases the secretion of total protein and of a specific type of glycoprotein from the lungs of the treated animals, in a manner that parallels the abn...

Pancreatic Function in the Reserpinized Rabbit—a Model for Cystic Fibrosis. I. Effect of Secretin

“…However, the effect of reserpine treatment on the output of the pancreatic juice does not appear to be as dramatic as the CF condition. For example, in reserpinized rats a 35% decrease in the p increatic juice was observed when treated animals were compaled with untreated controls during secretin stimulation (16). In these studies on reserpinized rabbits, only a 25% decrease in the output of the pancreatic juice during secretin stimulation was observed ( Table 1).…”

“…In these earlier studies altered secretory responses to CCK, secretin (16) and to other neurohormonal agents which elicit pancreatic function (15) were observed. Upon stimulation with CCK these investigators noted increases in both the concentration and the output of amylase and total protein in the pancreatic juice of fasted reserpine treated rats.…”

“…One such model is the chronically reserpinized rat. Rats treated for several days with reserpine develop morphologic and secretory changes in the submaxillary gland (9,11) and in the pancreas (6,16) which resemble those present in CF patients. The Na+ transport inhibitory factor, present in the saliva of CF patients (7) has been demonstrated in the saliva of reserpinized rats as well (13).…”

The Chronically Reserpinized Rat as an Animal Model for Cystic Fibrosis: I. Acute Effect of Isoproterenol and Pilocarpine upon Pulmonary Lavage Fluid

“…An animal model for CF developed by the chronic administration of reserpine to rats shows not only morphologic and secretory changes in the salivary glands (16,17,18,19) and pancreas (20), but also alterations in the protein content of pulmonary lavage fluids, involving a significant increase in the total protein content and in the absolute and relative amounts of a low molecular weight glycoprotein, which were also observed in lung lavage samples from patients with CF (28).…”

The Chronically Reserpinized Rat as a Model for Cystic Fibrosis: Abnormal Cl− Transport as the Basis for Reduced Salivary Fluid Secretion

“…The finding of abnormal C1-transport in the submandibular salivary gland of reserpine-treated rats is significant for two reasons: 1) The reserpine-treated rat has been used as an experimental animal model for cystic fibrosis on the basis ofwidespread exocrine gland disturbances resembling those of the human disease (13,19,20). Recent evidence has indicated that C1-permeability is abnormal in the sweat gland (15) and airways (16) of patients with cystic fibrosis.…”