Increased sensitivity of gastrin cells to gastric distension following antral denervation in the rat.

Abstract

1. Secretion of the antral hormone gastrin is increased by protein in the gastric lumen and by nervous reflexes. We have examined the relative importance of luminal and neuronal mechanisms, by lesioning the antral innervation using benzalkonium chloride. 2. Benzalkonium chloride was applied to the serosa of the antrum in anaesthetized rats. In some animals, a stainless-steel cannula was also implanted in the corpus. Animals were allowed 10 days to recover. Plasma gastrin was measured by radioimmunoassay and mRNAs encoding gastrin, somatostatin and histidine decarboxylase were measured by Northern blot. 3. Antral denervation was associated with gastric retention after fasting, and elevated plasma gastrin (28.4 +/- 7 pM compared with 7.6 +/- 1.0 pM in controls). When fasted control or denervated rats were refed, plasma gastrin increased 3-fold in both cases. A gastrin-releasing peptide antagonist inhibited the post-prandial rise in plasma gastrin in control rats, but had no effect in antrally denervated rats. 4. In fasted, antrally denervated rats with a gastric fistula, basal gastric acid secretion was depressed 3-fold, and plasma gastrin concentrations were similar to controls. 5. Distension of the stomach with peptone via a barostat attached to the gastric cannula (5 cm H2O, 30 min), produced 3-fold increases in plasma gastrin in both control and denervated rats. However, distension with a non-nutrient solution at pH 6.0 had no effect in controls, but increased gastrin to a similar extent to peptone in denervated rats; distension with 50 mM HCl had no effect in either control or denervated rats. 6. Somatostatin and gastrin mRNA abundances in the antrum were depressed by about 35% by antral denervation, but somatostatin mRNA in the corpus was unchanged; GAPDH mRNA abundance was unaffected by antral denervation. 7. The data suggest that luminal nutrient releases gastrin in the rat, in vivo, via activation of antral neurons secreting gastrin-releasing peptide, and that the antral innervation normally inhibits G-cell responses to non-nutrient distension of the stomach. After antral denervation, gastric distension with a non-nutrient solution is an adequate stimulus for gastrin release.