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

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.