AJP - Regulatory, Integrative and Comparative Physiology, Vol 261, Issue 5 1141-R1146, Copyright © 1991 by American Physiological Society
Gastric loads potentiate inhibition of food intake produced by a cholecystokinin analogue
G. J. Schwartz, L. A. Netterville, P. R. McHugh and T. H. Moran
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
We have proposed that cholecystokinin's (CCK) inhibition of gastric
emptying contributes to its ability to inhibit food intake. To directly
test this hypothesis in rats, the effect of the presence of a 5-ml gastric
saline load on the ability of a long-acting cholecystokinin analogue
U-67827E (0.1-10.0 nmol/kg) to inhibit intake of a 0.5 kcal/ml glucose
solution was measured. The CCK analogue alone inhibited intake at a
threshold dose of 2.5 nmol/kg. Although lower doses of the CCK analogue
alone had no effect on subsequent glucose intake, when combined with the
gastric load such doses did significantly inhibit intake. Thus the presence
of a gastric load reduced the threshold dose of the CCK analogue required
to inhibit intake. Furthermore, at suprathreshold doses, the peptide-load
combination suppressed intake more than the peptide alone. In addition,
administration of 0.5 and 5.0 nmol/kg doses of the CCK analogue inhibited
gastric emptying at 10, 20, and 30 min in a dose-dependent fashion. The CCK
analogue's inhibition of food intake and gastric emptying were reversed by
pretreatment with 100 micrograms/kg L364,718, indicating that the analogue
was having its effects by interacting with specific type A CCK receptors.
Together these data support the notion that CCK satiety derives from an
integration of the visceral afferent signals generated by CCK's promotion
of gastric distension and those produced directly by CCK.
