Changes in the exocrine pancreas secondary to altered small intestinal function in the CF mouse

The exocrine pancreas of the cystic fibrosis (CF) mouse (cftr(m1UNC)) is on ly mildly affected compared with the human disease, providing a useful mode l to study alterations in exocrine function. The CF mouse pancreas has simi lar to 50% of normal amylase levels and similar to 200% normal Muclin level s, the major sulfated glycoprotein of the pancreas. Protein biosynthetic ra tes and mRNA levels for amylase were not altered in CF compared with normal mice, and increases in Muclin biosynthesis and mRNA paralleled the increas ed protein content. Stimulated pancreatic amylase secretion in vitro and in vivo tended to be increased in CF mice but was not statistically significa nt compared with normal mice. We show for the first time that the CF mouse duodenum is abnormally acidic (normal intestinal pH = 6.47 +/-0.05; CF inte stinal pH = 6.15 +/-0.07) and hypothesize that this may result in increased signaling to the exocrine pancreas. There were significant increases in CF intestinal mRNA levels for secretin (310% of normal, P<0.001) and vasoacti ve intestinal peptide (148% of normal, P<0.05). Furthermore, CF pancreatic cAMP levels were 147% of normal (P<0.01). These data suggest that the CF pa ncreas may be chronically stimulated by cAMP-mediated signals, which in tur n may exacerbate protein plugging in the acinar/ductal lumen, believed to b e the primary cause of destruction of the pancreas in CF.