Mucosal gastrin receptor. VII. Up- and downregulation.

A series of experiments were performed to examine the long-term upregulation of the gastrin receptor and to explore the possibility of a short-term down regulation with regard to the time course of the trophic action of gastrin. Vagotomy or fasting was used to examine upregulation. Elevated serum gastrin levels observed postvagotomy are accompanied by an increase in gastrin binding capacity. Conversely, fasting caused a decline in serum gastrin and receptor levels; refeeding restored both values to normal levels. Cycloheximide was used to study the role of protein synthesis in the upregulation of gastrin receptors in vagotomized and refed rats, and it prevented the rise of gastrin binding capacity to either normal or above-normal values. This indicates that protein synthesis may play an integral part of receptor upregulation. Following the injection of gastrin-17, there was a short-term induction of downregulation. These results coupled with the maximal reduction of gastrin receptor 3 h after cycloheximide injection indicate that the gastrin receptor has a short half-life. Following the gastrin receptor interaction, the cellular response occurs at discrete periods and manifests itself as both down- and upregulation.