CANDIDATE CANINE ENTEROGASTRONES - ACID INHIBITION BEFORE AND AFTER VAGOTOMY

The relative contributions of several gut-derived peptides as enteroga strones known to be released in response to a fatty meal and to inhibi t acid secretion have not previously been compared directly. We determ ined the acid-inhibitory activities of increasing intravenous doses of several peptides before and after highly selective vagotomy (HSV) dur ing intragastric titration of a peptone meal in dogs. Before HSV, thre shold inhibitory doses of peptide YY (PYY), cholecystokinin (CCK), and secretin were 5, 7, and 10 pmol.kg(-1).h(-1), respectively, whereas n eurotensin, glucagonlike peptide-1 (GLP-1), and oxyntomodulin failed t o inhibit acid secretion at doses up to 1,000 pmol.kg(-1).h(-1). The c alculated dose producing 50% acid inhibition (ID50) Of secretin (62 pm ol.kg(-1).h(-1)) was one-half that of PW (128 pmol.kg(-1).h(-1)). Maxi mal (90%) acid inhibition was produced by 100 pmol.kg(-1).h(-1) secret in and 500 pmol.kg(-1).h(-1) PYY. The highest dose of CCK that did not cause vomiting (100 pmol.kg(-1).h(-1)) inhibited peptone-stimulated a cid output by only 60%. After HSV, 500 pmol.kg(-1).h(-1) PYY and 200 p mol.kg(-1).h(-1) CCK failed to inhibit acid output by more than 50%. T hreshold doses for inhibition by PW and CCK were 200 and 100 pmol.kg(- 1).h(-1), respectively. Secretin remained a potent inhibitor after HSV , with an ID50 Of 80 pmol.kg(-1).h(-1) and a threshold dose of 10 pmol .kg(-1).h(-1). HSV also failed to affect inhibition caused by somatost atin. This study has shown that PYY and secretin are somewhat more pot ent and efficacious inhibitors of acid secretion than CCK but that all three peptides are far more active than GLP-1, neurotensin, and oxynt omodulin. PW and CCK inhibit acid secretion in large part through vaga l innervation of the gastric fundus, but the inhibitory effects of sec retin are independent of fundic vagal innervation.