Regulation of pancreatic exocrine function in Otsuka Long-Evans Tokushima Fatty (OLETF) rats without gene expression of cholecystokinin-A receptor.

This work extends a recent observation that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show a congenital defect of the cholecystokinin (CCK)-A receptor gene. Expression of CCK-A receptor mRNA in the pancreas, small intestine and brain were not detected in OLETF rats by the reverse transcriptase polymerase chain reaction. In vitro studies showed that the maximal effective concentrations of neuromedin C, acetylcholine and secretin for stimulation of amylase secretion were comparable in both strains, but that CCK-stimulated amylase secretion was observed only in Long-Evans Tokushima Otsuka (LETO) rats. Intracellular cytosolic Ca2+ movement stimulated by acetylcholine and neuromedin C was similar in both strains. In vivo studies showed that the pancreatic secretions in response to secretin and acetylcholine were not impaired in OLETF rats. However, protein responses to neuromedin C and 2-deoxy-D-glucose were impaired in OLETF rats. The findings suggest that pancreatic exocrine functions in OLETF rats are regulated by all neural and peptidergic agents except CCK.