Cholecystokinin receptor antagonist MK-329 blocks intestinal fat-induced inhibition of meal-stimulated gastric acid secretion.
MK-329, a selective type A cholecystokinin (CCK) receptor antagonist, was given to dogs to test the hypothesis that CCK is one of the principal physiological enterogastrones mediating fat-induced decreases in gastric acid secretion. Gastric acid secretion in response to 300 mL 8% peptone meals was measured by intragastric titration to pH 5.5 in six awake dogs with chronic gastric, duodenal, and jejunal fistulas. Gastric emptying was measured by a dye-dilution technique. During the last hour of peptone stimulation, the intestine was perfused with either control solution or 20% lipid (Intralipid; Kabi Vitrum, Alamedo, CA) intraduodenally or intrajejunally. Compared with control perfusions, mean gastric acid outputs were decreased significantly after lipid perfusion of the duodenum (47% of control) and jejunum (24% of control). Similarly, mean gastric emptying rates were significantly less after lipid perfusion of the duodenum (56%) and jejunum (26%). Oral pretreatment with MK-329 (1 mg/kg) significantly reversed the inhibition of gastric acid output caused by lipid perfusion of the duodenum and jejunum, but fat-induced inhibition of gastric emptying was not significantly affected. These studies provide evidence for an important inhibitory role for CCK as an enterogastrone but do not implicate CCK as being important in fat-induced delayed gastric emptying of a liquid meal in dogs.
Lloyd
K C
KC
Department of Veterans Affairs, West Los Angeles Medical Center, California.
Maxwell
V
V
Kovacs
T O
TO
Miller
J
J
Walsh
J H
JH
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D020109:Devazepide; D004041:Dietary Fats / Q000494:pharmacology*; D004285:Dogs; D004435:Eating / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism*; D005746:Gastric Emptying / Q000187:drug effects; D005755:Gastrins / Q000097:blood; D007422:Intestines / Q000502:physiology*; D010461:Peptones; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D001570:Benzodiazepinones; D004041:Dietary Fats; D005755:Gastrins; D010461:Peptones; D011949:Receptors, Cholecystokinin; D020109:Devazepide