A. Higham et al., INCREASED SENSITIVITY OF GASTRIN CELLS TO GASTRIC DISTENSION FOLLOWING ANTRAL DENERVATION IN THE RAT, Journal of physiology, 503(1), 1997, pp. 169-175
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.