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Am J Physiol Gastrointest Liver Physiol 255: G685-G689, 1988;
0193-1857/88 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 255, Issue 5 685-G689, Copyright © 1988 by American Physiological Society

ARTICLES

Action of the cholecystokinin antagonist L364,718 on gastric emptying in the rat

T. Green, R. Dimaline, S. Peikin and G. J. Dockray
Physiological Laboratory, University of Liverpool, United Kingdom.

Cholecystokinin (CCK) is a potent inhibitor of gastric emptying. We have examined the effects of a novel potent peripheral CCK receptor antagonist (L364,718) on the action of endogenous and exogenous CCK octapeptide (CCK-8) on gastric emptying in the rat. In conscious gastric fistula rats, the recovery of liquid test meals of 3.0 ml (containing phenol red as a dilution marker) was determined over periods up to 8 min. Compared with saline, gastric emptying of solutions of peptone (4.5%), 50 mM HCl, and hyperosmolal saline was significantly delayed. The emptying of saline was also delayed by intravenous infusion of CCK-8 (400 pmol.kg-1.h-1). The CCK antagonist L364,718 reversed the effect of peptone in a dose-dependent manner and inhibited the response to exogenous CCK, but the emptying of physiological saline, 50 mM HCl, or hyperosmolal saline remained unchanged. A protease inhibitor (FOY-305) that is thought to release endogenous CCK by inhibiting negative feedback control by luminal proteases also delayed emptying, and this response was inhibited by L364,718. We conclude that CCK has a physiological role in the mediation of the effect of proteins on gastric emptying in the rat.


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