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Journal of Neuroscience, Vol 8, 3018-3024, Copyright © 1988 by Society for Neuroscience
Mechanisms of action of peripherally administered cholecystokinin octapeptide on brain stem neurons in the rat
HE Raybould, RJ Gayton and GJ Dockray
MRC Secretory Control Group, Physiological Laboratory, University of Liverpool, UK.
We have investigated the pathway and the mechanism by which cholecystokinin
octapeptide (CCK-8), given systemically, may influence the discharge of
brain stem neurons that have an input from the stomach. Extracellular
recordings were made from neurons in the nucleus of the solitary tract
(NTS), where vagal afferents terminate, and from neighboring regions of the
dorsal medial medulla. Gastric distension and CCK-8 injected
intra-aortically close to the stomach evoked either excitatory or
inhibitory responses that were abolished by cervical vagal section. In
animals from which the celiac/superior mesenteric ganglia were removed, or
the gastric antrum resected 2 weeks earlier, responses to gastric
distension and CCK-8 were maintained. The effects of CCK-8 are unlikely to
be secondary to changes in smooth muscle tone because CCK-8 decreased
pressure in the body of the stomach, while distension increased it.
Moreover, intravenous noradrenaline and vasoactive intestinal peptide had
effects similar to CCK-8 on intragastric pressure, but evoked different
patterns of responses from brain stem neurons. The results are consistent
with the idea that CCK-8 acts directly on vagal mechanoreceptive endings in
the gastric corpus wall. It is well known that peripheral administration of
CCK-8 influences short-term regulation of food intake. The effects
described here may reflect the pathway by which peripheral CCK influences
CNS function.
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