INCREASED SENSITIVITY OF GASTRIN CELLS TO GASTRIC DISTENSION FOLLOWING ANTRAL DENERVATION IN THE RAT

1. Secretion of the antral hormone gastrin is increased by protein in the gastric lumen and by nervous reflexes. We have examined the relati ve importance of luminal and neuronal mechanisms, by lesioning the ant ral 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 b y radioimmunoassay and mRNAs encoding gastrin, somatostatin and histid ine decarboxylase were measured by Northern blot. 3. Antral denervatio n was associated with gastric retention after fasting, and elevated pl asma gastrin (28.4 +/- 7 pM compared with 7.6 +/- 1.0 par in controls) . When fasted control or denervated rats were refed, plasma gastrin in creased 3-fold in both cases. A gastrin-releasing peptide antagonist i nhibited the post-prandial rise in plasma gastrin in control rats, but had no effect in antrally denervated rats. 4. In fasted, antrally den ervated rats with a gastric fistula, basal gastric acid secretion was depressed 3-fold, and plasma gastrin concentrations were similar to co ntrols. 5. Distension of the stomach with peptone via a barostat attac hed to the gastric cannula (5 cmH(2)O, 30 min), produced 3-fold increa ses in plasma gastrin in both control and denervated rats. However, di stension with a non-nutrient solution at pH 6.0 had no effect in contr ols, but increased gastrin to a similar extent to peptone in denervate d rats; distension with 50 mar HCl had no effect in either control or denervated rats. 6. Somatostatin and gastrin mRNA abundances in the an trum were depressed by about 35% by antral denervation, but somatostat in mRNA in the corpus was unchanged; GAPDH mRNA abundance was unaffect ed by antral denervation. 7. The data suggest that luminal nutrient re leases gastrin in the rat, in vivo, via activation of antral neurons s ecreting gastrin-releasing peptide, and that the antral innervation no rmally inhibits G-cell responses to non-nutrient distension of the sto mach. After antral denervation, gastric distension with a non-nutrient solution is an adequate stimulus for gastrin release.