Inhibition of gastrin release by gastric inhibitory peptide mediated by somatostatin

Abstract

The present studies were directed to examine the effect of gastric inhibitory peptide (GIP) on gastrin release and to determine the potential role of somatostatin in mediating this effect, utilizing rat antral mucosa in short-term tissue culture. Antral mucosa was incubated at 37 degrees C in Krebs-Henseleit buffer (pH 7.4) continuously gassed with 95% O2-5% CO2. Inclusion of carbachol (2.5 X 10(-6) M) in the culture medium increased media gastrin concentrations from 3.29 +/- 0.76 (SE) (control) to 6.77 +/- 0.76 ng/mg tissue prot (P less than 0.02). Rat antral mucosa was then incubated in the presence of GIP (10(-10) to 10(-7) M) to determine its effect on carbachol-stimulated gastrin release. GIP significantly inhibited carbachol-stimulated gastrin release into the culture media at all concentrations examined. To determine whether inhibition of carbachol-stimulated gastrin release by GIP was mediated by somatostatin, antral mucosa was incubated in the presence of carbachol, GIP (10(-10) to 10(-7) M), and specific antibodies to somatostatin in excess. Inclusion of antibodies to somatostatin in the culture medium abolished the capacity of GIP (10(9) to 10(-7) M) to inhibit carbachol-stimulated gastrin release. Results of these studies indicate 1) that GIP inhibits carbachol-stimulated gastrin release and 2) that, under the conditions of these experiments, GIP inhibition of gastrin release may be mediated locally through release of antral somatostatin.