Effect of cholecystokinin-octapeptide, caerulein, and pentagastrin on epithelial cell proliferation in the murine gallbladder.

The growth-promoting effect of cholecystokinin-octapeptide, caerulein, and pentagastrin on gallbladder mucosa was investigated in mice. The acute effects on deoxyribonucleic acid synthesis activity was explored with a [3H]thymidine pulse and autoradiography after subcutaneous injection of the polypeptides. The administration of a supramaximal dose of caerulein or of cholecystokinin-octapeptide induced a significant increase (p less than 0.01) in the nuclear uptake of [3H]thymidine by the gallbladder epithelial cells. The injection of pentagastrin had no effect. Implantation of osmotic minipumps was used for the chronic administration of submaximal doses of caerulein or pentagastrin. Using successive [3H]thymidine pulses and autoradiography, increases in labeling (p less than 0.01) and mitotic indices (p less than 0.05) were observed in the caerulein group, whereas pentagastrin had no effect. In addition, a morphometric method was used to determine the total epithelial cell number in the entire gallbladder after chronic administration of the peptides. A significant (p less than 0.01) epithelial cell hyperplasia was observed to occur after caerulein administration whereas pentagastrin given by the same route had no effect on the epithelial cell population. These data indicate that cholecystokininlike peptides promote epithelial growth in the gallbladder of mice.