Both afferent and efferent nerves are implicated in cholecytokinin motor actions in the small intestine of the rat

Cholecystokinin (CCK) regulates intestinal motility after being released by several luminal nutrients. However the mechanism of action of CCK is still not well known. The aim of our study was to establish the mechanism of act ion of CCK in the rat intestine using an in vivo model and focusing on the nervous pathways involved in the response as well as type of receptors. Ane sthetized rats were prepared with two strain-gauges, in duodenum and jejunu m, to record circular muscle motor activity. A group of animals was also pr epared with a catheter to infuse capsaicin inside the duodenum. Responses t o CCK-octapeptide (CCK-S) as well as to CCK agonists were studied. CCK-8 wa s also infused after CCK antagonists, atropine, hexamethonium or L-nitroarg inine. Results show that duodenal response to CCK-S is excitatory although inhibitory responses can be induced by gastrin. In the jejunum, CCK-8 induc es an inhibitory response that is mediated by both CCK-A and -B receptors. Excitatory responses to CCK-8 are due to stimulation of preganglionic recep tors while inhibitory responses are NO mediated through stimulation of post ganglionic CCK-B receptors, Capsaicin locally applied in duodenal mucosa si gnificantly decreased CCK-8 response, whereas mucosal exposure to lidocaine completely blocked CCK-8 response. In conclusion our results show that CCK response varies along the intestine according to the predominance of excit atory or inhibitory efferent innervation. Moreover, CCK-8 actions are media ted through both extrinsic and intrinsic afferent fibres. (C) 1999 Elsevier Science B.V. All rights reserved.