Postnatal development of the rat exocrine pancreas. II. Effects of protein-calorie malnutrition on amylase secretion and CCK receptor binding.

Malnutrition induces pancreatic atrophy and intracellular derangement, but its effects on cholecystokinin (CCK) receptors and the CCK-induced secretory response remain unclear. We used a rodent model to study the developmental effects of protein-calorie malnutrition on exocrine pancreatic function. Simultaneous experiments evaluated postnatal alterations in CCK-induced amylase response and receptor binding of pancreatic acini. At all postnatal ages, somatic and pancreatic weight of the malnourished rats was significantly below age-matched controls (p < 0.01). The malnourished rats showed a higher secretory response to CCK at 1 day of age and increased acinar sensitivity at 2 days. Maximal amylase secretion was significantly higher at 5 and 18 days (p < 0.05), but remained similar to that of the age-matched controls at 36 days. CCK receptor binding showed no significant changes at 1 and 2 days postnatally in comparison with controls. At 5 and 18 days, the affinity of the high-affinity state showed a twofold increase, while the capacity of the high-affinity state decreased by 40-55%. At the same time, the affinity of the low-affinity state increased significantly (p < 0.05), but the capacity of the low-affinity state was essentially unchanged. The acinar sensitivity of malnourished rats was consistently reduced between 5 and 36 days, which coincided with a reduction in spare receptors in the malnourished rats. In conclusion, the increased amylase secretory response at 1 and 2 days of age may be due to an adaptive response of endocrine function to maternal metabolic stress. The increased affinities of CCK receptors at 5 and 18 days may be associated with a higher secretory responsiveness, while the decreased spare receptors may contribute to a reduction in the acinar sensitivity. These results demonstrate that malnutrition induces changes in CCK binding and its secretory response.