Development and age-related changes in pancreatic cholecystokinin receptors and duodenal cholecystokinin in guinea pigs

We have investigated the changes associated with development and aging on the interrelationships between cholecystokinin (CCK) and the pancreas in the guinea pig. Three groups (1 month old, 1 year old, and 3 years old) of male guinea pigs were sacrificed while feeding in order to measure food-stimulated levels of CCK in blood and in duodenal mucosa by radioimmunoassay (RIA), as well as the pancreatic concentrations of CCK receptors. Systemic blood concentrations of CCK did not change with age. However, the concentration and content of CCK in duodenal mucosa increased more than 3-fold with age. A single class of high-affinity (K_D≤0.1 nM) CCK-receptor was found on the pancreatic membranes. The concentration (fmol/mg protein) of these receptors significantly diminished by one-half with increasing age. We als found an apparently similar fall in the receptor-binding affinity, but the difference was not significant. We conclude that in the guinea pig, duodenal content of CCK increases so as to compensate for the decreasing concentration of pancreatic CCK receptors, or, perhaps, vice versa. The diminished exocrine function of the pancreas, seen with increasing age, may well reflect both the diminished number of CCK-receptors and the reduction of pancreatic acinar cells.