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-Trp8]-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.
Department of Medicine, University of Toronto, Ontario, Canada.
L C
LC
Fung
G R
GR
Greenberg
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D004435:Eating; D005744:Gastric Acid; D005755:Gastrins / Q000097:blood*; D009116:Muscarine / Q000378:metabolism*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D019518:Postprandial Period; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D005755:Gastrins; D018727:Muscarinic Antagonists; D013004:Somatostatin; D001285:Atropine; D009116:Muscarine; D009853:Omeprazole