Gastrin has two principal biological effects: stimulation of acid secretion from gastric parietal cells and stimulation of mucosal growth in the acid-secreting part of the stomach. Circulating gastrin regulates the increase in acid secretion that occurs during and after meals. Gastrin also stimulates mucosal growth in the stomach. Exogenously administered gastrin causes increased cell division in the proliferative zone that lies between the surface cells and the gastric glands in the acid-secreting mucosa. The newly formed cells undergo differentiation into surface epithelial cells, parietal cells and gastric enterochromaffin-like cells. Furthermore, the increased mucosal proliferation that occurs with refeeding after a period of fasting may be mediated by gastrin since refeeding stimulates gastrin production and a parallel increase in mucosal DNA synthesis. Both food and gastrin cause a rapid increase in cell division and an increase in gastric ornithine decarboxylase mRNA in fasting rats. In preliminary immunoneutralization experiments, the stimulation of ornithine decarboxylase produced by food was inhibited by gastrin antibody. The sustained inhibition of gastric acid secretion obtained by surgery or with antisecretory drug therapy results in hypergastrinaemia associated with increased gastric mucosal cell proliferation. A good correlation between gastric enterochromaffin-like cell density and circulating gastrin concentrations has been found under these conditions as well as during infusions of exogenous gastrin. Trophic effects of gastrin have also been reported for the colon, duodenum and pancreas, but chronic hypergastrinaemia does not appear to produce hyperplasia of these organs. It can be concluded, therefore, that gastrin acts as a physiological stimulant of both gastric acid secretion and gastric mucosal growth and mediates the gastric mucosal proliferation that occurs in response to feeding and hypochlorhydria.
