Mechanism of action of cholecystokinin on intestinal blood flow; interactions with opioid peptides and vasoactive intestinal peptide.

The effects of local administration of CCK-OP on mesenteric blood flow was studied in anaesthetized dogs using an electromagnetic flowmeter and interactions with the opioid peptides and VIP examined. CCK-OP was found to enhance enteral blood flow and tissue metabolism. Investigations with pharmacological antagonists showed that the vasoregulatory effect was exerted neurogenically, by influencing the activities of sympathetic alpha 2 adrenergic, dopaminergic, cholinergic, muscarinergic and nicotinic neurones. The flow-increasing action of CCK-OP was enhanced by D-Met2-NleS5-enkephalinamide; the effect was additive and partially blocked by naloxone. D-Met2-Pro5-enkephalinamide blocked the increases caused by CCK-OP in blood flow and tissue acetylcholine levels. The blockade was not competitive and could be totally eliminated by naloxone. VIP blocked the flow-increasing effect of CCK-OP by a non-competitive mechanism. The results provide data on the peptidergic regulatory mechanisms of the mesenteric circulation.