Regulation of somatostatin-14 and -28 secretion by gastric acid in dogs: differential role of cholecystokinin.
BACKGROUND
Prosomatostatin-derived peptides include two principle bioactive molecular forms, somatostatin 28 (S-28) and somatostatin 14 (S-14). This study examined whether there is a functional relationship between gastric acid secretion and the release of S-28 and S-14 into the circulation.


METHODS
In conscious dogs with gastric and duodenal cannulas, S-28 and S-14 responses, measured after extraction of acidified plasma and separation by gel chromatography, were evaluated by administration of nutrients and acid-inducing secretagogues without and with omeprazole.


RESULTS
Ingestion of a solid meal caused equivalent plasma elevations of S-28 and S-14, whereas infusions of histamine and gastrin selectively increased plasma S-14. Omeprazole decreased meal-stimulated S-28 (-67% +/- 8%; P < 0.01) and S-14 (-56 +/- 9%; P < 0.01) and abolished S-14 increases to histamine and gastrin. Intraduodenal perfusions of a liquid protein meal increased S-28 above S-14, comprising approximately 71% of total somatostatin-like immunoreactivity released, and omeprazole suppressed S-28 (-87% +/- 5%; P < 0.01) without influencing S-14. Similar responses occurred after exogenous cholecystokinin. Moreover, pretreatment of the intraduodenal protein meal with the cholecystokinin-A receptor antagonist MK-329 abolished increases of S-28 and S-14 and caused a further twofold increase of gastric acid (P < 0.025).


CONCLUSIONS
In the fed state, gastric acid causes direct release of S-14 from the stomach, but the acid-dependent component of S-28 secretion requires cholecystokinin as a cofactor. Negative feedback regulation between somatostatin and gastric acid secretory responses to nutrients may include S-28 modulated, in part, by cholecystokinin.
Greenberg
G R
GR
Department of Medicine, University of Toronto, Canada.
Fung
L
L
Pokol-Daniel
S
S
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000502:physiology*; D020109:Devazepide; D004044:Dietary Proteins / Q000494:pharmacology; D004285:Dogs; D004435:Eating; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005744:Gastric Acid / Q000502:physiology*; D005755:Gastrins / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D013004:Somatostatin / Q000378:metabolism*; D053561:Somatostatin-28
D001570:Benzodiazepinones; D004044:Dietary Proteins; D005217:Fat Emulsions, Intravenous; D005755:Gastrins; D013004:Somatostatin; D053561:Somatostatin-28; D006632:Histamine; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide