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

Abstract

Summaryby CF, ~ancreatic secretions have not been as extensively studiedPancreatic juice was collected from rabbits treated with reserpine and from untreated controls. The volume of pancreatic juice secreted, flow rate and the bicarbonate output were all significantly reduced in the treated animals during both spontaneous flow and during secretin-stimulated flow. On the other hand, the total protein concentration, the amylase activity and the calcium concentration of the pancreatic juice were all significantly elevated in the treated animals. The elevation in the total protein concentration appeared to be due to both increased amounts of protein and decreased amounts of water. Of particular interest was that secretin stimulation caused the same % increase in the flow rate and output of pancreatic juice in both control and reserpine treated rabbits. he method-by which fluid is secreted by-the treated animal, therefore, appeared to be depressed at all times and under all conditions. Decreased volumes of pancreatic juice, a decreased bicarbonate output and increased concentrations of protein and calcium are found in this model and are consistent with clinical findings present in the pancreatic secretions obtained from individuals with cystic fibrosis. Therefore, the similarities between secretions of the reserpine treated rabbit and those observed in the cystic fibrosis patient support its use as an experimental model for investigating the abnormal pancreatic secretions in this disease. SpeculationRabbits treated with reserpine for 7 days secrete smaller volumes of pancreatic juice at lower rates of flow during both spontaneous and secretin-stimulated conditions. This juice contains elevated levels of total protein, enzymes, calcium and smaller amounts of bicarbonate. Because these alterations are common in patients with CF, the reserpine-treated rabbit appears to be a good model to investigate the perturbations taking place in the pancreas during the course of this disease.The study of cystic fibrosis (CF) has been hampered by the lack of an equivalent disease in a lower species. For this reason attempts have been made to pharmacologically perturb the exocrine secretions of an experimental animal to the point where they resemble what is seen in this disease (8,10). 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). In addition, this treatment increases the pulmonary secretion of phospholipids (14), total protein (21) and of a specific type of glycoprotein which is also present in lung lavages of CF patients (21). These alterations seem to indicate that reserpinization creates a generalized exocrine gland dysfunction resulting in a fairly complete animal model with which this d...

Altered Bicarbonate Reabsorption in the Pancreas of Reserpine-Treated Rabbits—a Model for Cystic Fibrosis

“…It is important to note, however, that despite the presence of the factor, the total bicarbonate output in the juice of reserpinized rabbits was significantly less than that observed for controls (Table 2). This observation confirms previous studies made in reserpinized rabbits (17) and rats (14). By contrast, the bicarbonate ouput after retroperfusion with substances containing known transport inhibitory properties was elevated over that of controls (Table 2); thus, the reduced bicarbonate output must have been secondary to the reduced volume of pancreatic juice secreted by the reserpinized animals (Table 1) (14,16,17).…”

“…This is due to a positively charged transport inhibitory factor (13). The pancreas of reserpine-treated rats and rabbits secrete reduced amounts of juice which contains elevated amounts of protein but a decreased bicarbonate output (14,17). In this study, the pancreatic juice secreted by treated rabbits was also shown to contain a decreased bicarbonate output (Table 1) but an elevated bicarbonate concentration (Fig.…”

“…Reserpinized animals received seven daily intramuscular injections at a dose of 0.5 mg/kg of body weight. After a 24-h fast on the seventh day of treatment, each animal was anesthetized with 1.0 ml/kg of Dial-Urethane (Ciba Pharmaceutical Co., Summit, NJ), a tracheostomy was performed and the femoral artery and vein were cannulated (17). An incision was made in the animal's abdomen and the main pancreatic duct was identified and cannulated.…”

“…It has also been demonstrated that the elevated salivary sodium observed in reserpinized rats is due to a transport inhibitory factor with similar properties to the factor found in both the salivary and sweat glands of patients with CF (13). More recently, the pancreatic juice of reserpine-treated rabbits has been studied and shown to resemble the pancreatic secretions produced by patients with CF as well (16,17). This paper represents a continuation of these studies and demonstrates that in addition to low flow rates and a reduced bicarbonate output, the pancreatic juice of reserpinized rabbits also contains a transport inhibitory factor which perturbs the reabsorption of bicarbonate across the ductal system of this gland.…”

Pancreatic Secretion by the Anaesthetized Rabbit in Response to Secretin, Cholecystokinin, and Carbachol

“…Early studies in anaesthetized animals showed it to possess a true spontaneous secretion (5), which could be augmented by vagal stimulation or intravenous acetylcholine (6). Between 1965 and the present, a number of studies have been published on anaesthetized rabbit, in which some aspects of pancreatic electrolyte secretion have been measured (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). In these studies, very considerable variations in the volume and composition of spontaneous and secretin-stimulated pancreatic juice are recorded, while in only four has the effect of CCK on fluid secretion been briefly mentioned (9,13, 16,18).…”