Dual effects of cholecystokininoctapeptide on duodenal motility of urethane-anesthetized rats

Intravenous administration of cholecystokinin octapeptide (CCK-8) to urethane-anesthetized rats produced both inhibitory and excitatory effects on intestinal motility. The inhibitory effect, evident as a transient relaxation or inhibition of distension-in-duced reflex contractions, was abolished by adrenoreceptor blockade, guanethidine pretreatment or removal of the celiac ganglion complex, but was hexamethonium- and atropine-insen-sitive. The excitatory action of CCK-8 was atropine- and hexa-methonium-sensitive, while being unaffected by guanethidine pretreatment. Ligation experiments indicated that the excitatory effect of CCK-8 originates from a stimulant action on structures in the upper duodenum/pylonc sphincter from which a propa-gated contraction travels to the distal duodenum. We conclude that i.v. CCK-8 inhibits small intestinal motility by directly acti-vating sympathetic neurons in the celiac ganglion and initiates a propagated form of intestinal motility by stimulating neural ele-ments in the upper part of the small intestine. CCK is a well established gut hormone, reported to be present in several forms in various mammalian species (Dockray, 1977, 1988; Rehfeld et aL, 1979). A common feature ofaction of CCK-like peptides on the intestine of various species is that the sulphated form of the C-terminal octapeptide (CCK-8) is the smallest fragment having full biologic activity (Dockray, 1988). In the gut, the highest concentrations of CCK-like immuno-reactivity are found in the duodenum and proximal jejunum where they are contained in a specific class of endocrine cell