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 action 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. Anesthetized rats were prepared with two strain-gauges, in duodenum and jejunum, to record circular muscle motor activity. A group of animals was also prepared with a catheter to infuse capsaicin inside the duodenum. Responses to CCK-octapeptide (CCK-8) as well as to CCK agonists were studied. CCK-8 was also infused after CCK antagonists, atropine, hexamethonium or L-nitroarginine. Results show that duodenal response to CCK-8 is excitatory although inhibitory responses can be induced by gastrin. In the jejunum, CCK-8 induces an inhibitory response that is mediated by both CCK-A and -B receptors. Excitatory responses to CCK-8 are due to stimulation of preganglionic receptors while inhibitory responses are NO mediated through stimulation of postganglionic CCK-B receptors. Capsaicin locally applied in duodenal mucosa significantly 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 excitatory or inhibitory efferent innervation. Moreover, CCK-8 actions are mediated through both extrinsic and intrinsic afferent fibres.
Department of Cell Biology and Physiology, Universitat Autonoma of Barcelona, Bellaterra, Spain.
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Giralt
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Vergara
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism*; D020109:Devazepide / Q000494:pharmacology; D004386:Duodenum / Q000294:innervation / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D007583:Jejunum / Q000294:innervation / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism*; D009476:Neurons, Efferent / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D012844:Sincalide / Q000378:metabolism / Q000494:pharmacology; D013758:Tetragastrin / Q000031:analogs & derivatives / Q000494:pharmacology
D000779:Anesthetics, Local; D001570:Benzodiazepinones; D005755:Gastrins; D006727:Hormone Antagonists; D009842:Oligopeptides; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C063897:A 71378; C066278:A 71623; D019335:Nitroarginine; C058121:L 365260; D018738:Hexamethonium; D001285:Atropine; D002766:Cholecystokinin; D008012:Lidocaine; D020109:Devazepide; D012844:Sincalide