Candidate canine enterogastrones: acid inhibition before and after vagotomy.
The relative contributions of several gut-derived peptides as enterogastrones known to be released in response to a fatty meal and to inhibit acid secretion have not previously been compared directly. We determined the acid-inhibitory activities of increasing intravenous doses of several peptides before and after highly selective vagotomy (HSV) during intragastric titration of a peptone meal in dogs. Before HSV, threshold inhibitory doses of peptide YY (PYY), cholecystokinin (CCK), and secretin were 5, 7, and 10 pmol.kg-1.h-1, respectively, whereas neurotensin, glucagon-like peptide-1 (GLP-1), and oxyntomodulin failed to inhibit acid secretion at doses up to 1,000 pmol.kg-1.h-1. The calculated dose producing 50% acid inhibition (ID50) of secretin (62 pmol.kg-1.h-1) was one-half that of PYY (128 pmol.kg-1.h-1). Maximal (90%) acid inhibition was produced by 100 pmol.kg-1.h-1 secretin 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 acid output by only 60%. After HSV, 500 pmol.kg-1.h-1. PYY and 200 pmol.kg-1.h-1 CCK failed to inhibit acid output by more than 50%. Threshold doses for inhibition by PYY 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 somatostatin. This study has shown that PYY and secretin are somewhat more potent and efficacious inhibitors of acid secretion than CCK but that all three peptides are far more active than GLP-1, neurotensin, and oxyntomodulin. PYY and CCK inhibit acid secretion in large part through vagal innervation of the gastric fundus, but the inhibitory effects of secretin are independent of fundic vagal innervation.
Lloyd
K C
KC
Research Service, Department of Veterans Affairs, West Los Angeles Medical Center, California, USA.
Amirmoazzami
S
S
Friedik
F
F
Heynio
A
A
Solomon
T E
TE
Walsh
J H
JH
D000821:Animal Feed; D000818:Animals; D002766:Cholecystokinin / Q000502:physiology*; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides / Q000502:physiology; D053772:Oxyntomodulin; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology / Q000502:physiology*; D011184:Postoperative Period; D017186:Titrimetry; D014628:Vagotomy / Q000379:methods
D053772:Oxyntomodulin; D010455:Peptides; D019894:Peptide YY; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin