Candidate canine enterogastrones: acid inhibition before and after
vagotomy.
Lloyd, K. C. K., S. Amirmoazzami, F. Friedik, A Heynio, T. E. Solomon,
and J. H. Walsh.
Research and Medical Services, Department of Veterans Affairs, West
Los Angeles Medical Center, and the Departments of Physiology and
Medicine, School of Medicine and CURE: VA/UCLA Digestive Disease Core
Center, University of California, Los Angeles, CA 90073
APStracts 3:0261G, 1996.
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 PYY, CCK, and
secretin were 5, 7, and 10 pmol/kg/h, respectively, while
neurotensin, glucagon-like peptide-1, and oxyntomodulin failed to
inhibit acid secretion at doses up to 1000 pmol/kg/h. The calculated
ID50 of secretin (62 pmol/kg/h) was half that of peptide YY (128
pmol/kg/h). Maximal (90%) acid inhibition was produced by 100
pmol/kg/h secretin and 500 pmol/kg/h PYY. The highest dose of CCK
that did not cause vomiting (100 pmol/kg/h) inhibited peptone
-stimulated acid output by only 60%. After HSV, 500 pmol/kg/h PYY and
200 pmol/kg/h CCK failed to inhibit acid output by more than 50%.
Threshold doses for inhibition by PYY and CCK were 200 and 100
pmol/kg/h, respectively. Secretin remained a potent inhibitor after
HSV, with an ID50 of 80 pmol/kg/h and a threshold dose of 10
pmol/kg/h. HSV also failed to affect inhibition caused by
somatostatin. This study has shown that peptide YY and secretin are
somewhat more potent and efficacious inhibitors of acid secretion
than CCK, but that all 3 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.
Received 13 November 1995; accepted in final form 27 November
1996.
APS Manuscript Number G486-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996