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Somatostatin-containing cells have been shown to be in close anatomic proximity to gastrin-producing cells in rat antral mucosa. The present studies were directed to examine the effect of secretin on carbachol-stimulated gastrin release and to assess the potential role of somatostatin in mediating this effect. Rat antral mucosa was cultured at 37 degrees C in Krebs-Henseleit buffer, pH 7.4, gassed with 95% O2-5% CO2. After 1 h the culture medium was decanted and mucosal gastrin and somatostatin were extracted. Carbachol (2.5 X 10(-6) M) in the culture medium increased gastrin level in the medium from 14.1 +/- 2.5 to 26.9 +/- 3.0 ng/mg tissue protein (P less than 0.02), and decreased somatostatin-like immunoreactivity in the medium from 1.91 +/- 0.28 to 0.62 +/- 0.12 ng/mg (P less than 0.01) and extracted mucosal somatostatin-like immunoreactivity from 2.60 +/- 0.30 to 1.52 +/- 0.16 ng/mg (P less than 0.001). Rat antral mucosa was then cultured in the presence of secretin to determine its effect on carbachol-stimulated gastrin release. Inclusion of secretin (10(-9)-10(-7) M) inhibited significantly carbachol-stimulated gastrin release into the medium, decreasing gastrin from 26.9 +/- 3.0 to 13.6 +/- 3.2 ng/mg (10(-9) M secretin) (P less than 0.05), to 11.9 +/- 1.7 ng/mg (10(-8) secretin) (P less than 0.02), and to 10.8 +/- 4.0 ng/mg (10(-7) M secretin) (P less than 0.02). Secretin (10(-7) and 10(-8) M) also increased concomitantly culture medium somatostatin concentration. To determine whether secretion inhibition of carbachol-stimulated gastrin release was mediated by somatostatin, antral mucosa was cultured with carbachol, secretin (10(-9)-10(-7) M), and antibodies to somatostatin. Inclusion of somatostatin antibodies in the culture medium abolished the capacity of secretin (10(-7) and 10(-8) M) to inhibit carbachol-stimulated gastrin release. Results of these studies indicate (a) that secretin inhibits carbachol-stimulated gastrin release and (b) that under the conditions of these experiments secretin inhibition of gastrin release is mediated, at least in part, locally through release of antral somatostatin.

Inhibition of gastrin release by secretin is mediated by somatostatin in cultured rat antral mucosa.