Inhibition by CCK of ascending contraction elicited by mucosal stimulationin the duodenum of the rat

CCK released by intraluminal stimuli modifies duodenal activity contributin g to a decrease in gastric emptying. However, the neural mechanisms by whic h CCK controls motility are not well known. The aim of this study was to in vestigate the interaction between CCK and the enteric nervous system throug h the study of the effects of CCK-8 on ascending excitation. Anaesthetized Sprague-Dawley rats were prepared with a strain-gauge sutured to the duoden um wall. An electrode holder was placed in the duodenum lumen to elicit asc ending contraction. Electrical field stimulation of the duodenal mucosa (4 Hz, 0.6 ms, 30 V) induced an ascending excitation which was blocked by hexa methonium (10 mg kg(-1); n=5) and atropine (0.3 mg kg(-1); n=5), but enlarg ed by L-NNA (10(-5) mol kg(-1); n=5). CCK-8 (3 x 10(-9) mol kg(-1) 10 min(- 1)) blocked ascending excitation and an inhibition of the induced phasic ac tivity was observed instead (n=18). Individually, none of the CCK receptor antagonists (L-364 718 and L-365 260) (3 x 10(-7) mol kg(-1); n=6 each) blo cked the inhibition of ascending excitation induced by CCK-8. However, simu ltaneous infusion of both antagonists abolished CCK-8 effect on electrical stimulation (n=5). Similarly, none of the CCK-8 agonists (A-71623, A-71378, gastrin) modified the ascending excitation. In contrast, the simultaneous infusion of A-71623 and CCK-4 (n=4) induced an effect similar to CCK-8. In conclusion, CCK-8 blocked ascending contraction elicited by electrical fiel d stimulation of duodenal mucosa by means of simultaneous activation of CCK -A and CCK-B receptors.