Inhibition by CCK of ascending contraction elicited by mucosal stimulation in the duodenum of the rat.
CCK released by intraluminal stimuli modifies duodenal activity contributing to a decrease in gastric emptying. However, the neural mechanisms by which CCK controls motility are not well known. The aim of this study was to investigate the interaction between CCK and the enteric nervous system through the study of the effects of CCK-8 on ascending excitation. Anaesthetized Sprague-Dawley rats were prepared with a strain-gauge sutured to the duodenum wall. An electrode holder was placed in the duodenum lumen to elicit ascending contraction. Electrical field stimulation of the duodenal mucosa (4 Hz, 0.6 ms, 30 V) induced an ascending excitation which was blocked by hexamethonium (10 mg kg-1; n=5) and atropine (0.3 mg kg-1; n=5), but enlarged by L-NNA (10(-5) mol kg-1; n=5). CCK-8 (3 ¿ 10(-9) mol kg-1 10 min-1) blocked ascending excitation and an inhibition of the induced phasic activity was observed instead (n=18). Individually, none of the CCK receptor antagonists (L-364 718 and L-365 260) (3 ¿ 10(-7) mol kg-1; n=6 each) blocked the inhibition of ascending excitation induced by CCK-8. However, simultaneous 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 field stimulation of duodenal mucosa by means of simultaneous activation of CCK-A and CCK-B receptors.
Giralt
M
M
Department of Cell Biology, Physiology and Immunology, Universität Autònoma de Barcelona, Spain.
Vergara
P
P
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003864:Depression, Chemical; D020109:Devazepide / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D017615:Enteric Nervous System / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005755:Gastrins / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010528:Peristalsis / Q000187:drug effects*; D010646:Phentolamine / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000494:pharmacology; D013758:Tetragastrin / Q000031:analogs & derivatives / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D001570:Benzodiazepinones; D004791:Enzyme Inhibitors; D005755:Gastrins; D018733:Nicotinic Antagonists; D009842:Oligopeptides; D010276:Parasympatholytics; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D018005:Receptors, Vasoactive Intestinal Peptide; D013758:Tetragastrin; C048507:vasoactive intestinal peptide, 4-chloro-Phe(6)-Leu(17)-; C063897:A 71378; C066278:A 71623; C075264:A 63387; D019335:Nitroarginine; C058121:L 365260; D014660:Vasoactive Intestinal Peptide; D018738:Hexamethonium; D001285:Atropine; D002766:Cholecystokinin; D011433:Propranolol; D020109:Devazepide; D012844:Sincalide; D010646:Phentolamine