Altered bicarbonate reabsorption in the pancreas of reserpine-treated rabbits--a model for cystic fibrosis.

Abstract

Summary: Pancreatic juice was collected from rabbits treated for 7 days with reserpine as well as from untreated controls. In treated rabbits, the volume of pancreatic juice secreted (0.94 ± 0.31 mg) and the maximum pancreatic juice flow rates (66.1 ± 7.1 mg/ (min·g)ffdpw) were both significantly less (p < 0.005) than observed in control animals (1.60 ± 0.24 mg and 98.3 ± 15 mg/(min·g)ffdpw). The bicarbonate concentration of the juice obtained from reserpinized rabbits was elevated at all flow rates when compared to the juice obtained from controls. When saliva obtained from patients with CF was retroperfused into the pancreatic ductal system of a control rabbit, the resultant pancreatic juice contained an elevated bicarbonate concentration at every given flow rate. In addition, 1 h after retroperfusion, bicarbonate output was elevated by 15% despite a reduction in pancreatic juice volume as compared to unretroperfused controls. When pancreatic juice obtained from reserpine-treated rabbits was retroperfused into the ductal system of a control rabbit's pancreas, an elevation in the bicarbonate concentration also resulted. In addition, 1 h after retroperfusion with reserpinized pancreatic juice, the bicarbonate output increased by 18% whereas the volume of pancreatic juice secreted during this period of time remained unchanged as compared to controls. No alteration in pancreatic bicarbonate, pancreatic juice volume, or flow rate was observed after retroperfusion with either saline, saliva obtained from control patients or pancreatic juice obtained from control rabbits. The pancreatic juice secreted by reserpinized rabbits, therefore, appeared to contain some type of factor that altered the reabsorption of bicarbonate. This pancreatic factor also appeared to be positively charged because its transport inhibitory properties were lost when the reserpinized juice was mixed with the polyanion heparin (500 U/ml) before retroperfusion. Despite these observations, the pancreatic bicarbonate output of treated animals was significantly less than that of controls both 30 min (P < 0.005) and 60 min (P < 0.010) after secretin stimulation. It is believed that this finding is secondary to a 41% reduction in the volume of pancreatic juice secreted by treated animals. Because the reserpine-treated rabbit has been proposed as a valid model for studying CF, this study proposes that a similar transport inhibitory factor might also be present in the pancreatic secretions of patients with this disease.