Somatostatin-14 modulates acid-dependent inhibition of meal-stimulated gastrin via muscarinic pathways in dogs

Intraluminal antral acidification inhibits gastrin and stimulates somatostatin-14 (S-14) release, but a functional relationship in the postprandial state has not been established. To examine whether meal-stimulated S-14 mediates inhibition of gastrin release by gastric acid, the effects of omeprazole on circulating levels of S-14 separated from S-28 by gel permeation chromatography, and gastrin were measured without and with atropine in dogs. Compared to controls, pretreatment with omeprazole decreased postprandial plasma levels of S-14 and S-28 (both P < 0.01) and increased gastrin (P < 0.001). Atropine selectively converted the S-14 response after omeprazole to a peak sixfold increase 40 min after meal ingestion (P < 0.001), which was also significantly above S-14 values after atropine alone and controls, but reduced plasma levels of S-28 and gastrin to baseline. Infusions of the somatostatin analogue, cyclo-[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(BZL)] increased postprandial gastrin twofold above controls (P < 0.05), and when administered after omeprazole reversed the inhibition of gastrin by atropine, without altering S-14 levels. In contrast, infusions of S-14, which simulated S-14 levels after omeprazole-atropine, and of [D-Trp(8)]-S-14, which abolished meal-stimulated S-14 responses, did not alter postprandial elevations of plasma gastrin. This study suggests that in conscious dogs muscarinic inhibitory pathways selectively regulate S-14 secretion, are amplified at neutral gastric pH and reciprocally link S-14 to gastrin secretion in the gastric phase of meal ingestion. Postprandial regulation of gastrin release by S-14 includes neurocrine interactions with muscarinic receptor activation; endocrine or paracrine regulation seem less likely. (C) 1998 Elsevier Science B.V.