POSTNATAL-DEVELOPMENT OF THE RAT EXOCRINE PANCREAS .1. ALTERATIONS INHIGH-AFFINITY AND LOW-AFFINITY CHOLECYSTOKININ RECEPTORS AND ENZYME-SECRETION

We tested the hypothesis that postnatal alterations in cholecystokinin (CCK) receptors are associated with developmental changes in enzyme s ecretory response. We used simultaneous measurements of CCK receptor b inding and amylase release in pancreatic acini isolated from rat pups at various ages (1, 2, 5, 6, 18, and 36 days). CCK receptor binding wa s analyzed using the LIGAND program. The affinity of the high-affinity state increased postnatally at 18 and 36 days (p < 0.05); the capacit y of the high-affinity state also increased at 2 days (p < 0.05) then declined sequentially up to 36 days. The affinity of the low-affinity state increased postnatally reaching statistical significance at 5 day s; the capacity of the low-affinity state increased twofold at 2 days, reaching statistical significance at 5 days (p < 0.05); this was foll owed by a slight decrease at 36 days. At 1 day postnatally a small amy lase response occurred (p < 0.05), but no dose-dependent response was observed. A significant CCK dose-dependent secretory response occurred at all other ages. Maximal amylase release was highest at 18 days (p, < 0.05). CCK doses required to stimulate maximal amylase release were 20, 2, 1, 0.2 and 0.4 nM at 2, 5, 6, 18, and 36 days, respectively. T he receptor occupancy rates for high-and low affinity states decreased sequentially between 2 and 18 days of age, when maximal amylase relea se occurred. These data suggest that more spare receptors become avail able with increasing postnatal age. We conclude that postnatal alterat ions of both high- and low-affinity states of CCK receptors in pancrea tic acini are associated with developmental changes in enzyme secretor y response to CCK. An increase in the affinity of high-affinity state and the capacity of the low-affinity state may enhance acinar sensitiv ity to CCK.