Serotonin type-3 receptors mediate cholecystokinin-induced satiation through gastric distension.
We have previously shown that serotonin type-3 (5-HT3) receptors mediate cholecystokinin (CCK)-induced satiation and that this effect is dependent on postoropharyngeal feedback. However, the independent contributions of gastric and intestinal feedback in 5-HT3 receptor mediation of suppression of food intake by CCK have not been determined. Using a sham-feeding preparation combined with intraduodenal sucrose infusion, we show that blockade of 5-HT3 receptors by ondansetron (1 mg/kg ip) had no effect on suppression of sham feeding by intraduodenal 15% sucrose infusion (4 ml/10 min), CCK (2 microg/kg ip) administration, or the combination of the two treatments. In separate experiments consisting of either sham-feeding rats that received gastric distension with the use of a balloon or real-feeding rats whose stomachs were distended using gastric loads of saline after the occlusion of the pylorus, we tested the hypothesis that gastric feedback signals are necessary for activation of 5-HT3 receptors. Ondansetron significantly attenuated suppression of sham sucrose intake after a 10-ml gastric balloon distension (30.5 +/- 2.2 vs. 20.2 +/- 2.2 ml, respectively) and gastric distension combined with CCK (21.9 +/- 1.4 vs. 12.0 +/- 1.7 ml, respectively). When intestinal feedback was eliminated in a real-feeding paradigm by closing the pylorus using a cuff preparation, ondansetron attenuated suppression of sucrose intake produced by a 10-ml saline gastric load (6.8 +/- 0.7 vs. 4.2 +/- 0.4 ml, respectively). Finally, when CCK (1 microg/kg) was administered in combination with a 5-ml saline gastric load in a real-feeding preparation, ondansetron significantly attenuated suppression of sucrose intake by CCK (9.0 +/- 0.9 vs. 6.3 +/- 0.5 ml, respectively), as well as the enhanced suppression of intake by CCK plus gastric load (6.9 +/- 0.6 vs. 4.6 +/- 0.5 ml, respectively). These findings demonstrate that CCK-induced activation of 5-HT3 receptors requires gastric, but not intestinal feedback.
Hayes
Matthew R
MR
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA 16802, USA. mrh212@psu.edu
Chory
Fiona M
FM
Gallagher
Claire A
CA
Covasa
Mihai
M
D000818:Animals; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D006815:Hunger / Q000502:physiology*; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012528:Satiety Response / Q000502:physiology*; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013270:Stomach / Q000502:physiology*; D013395:Sucrose
D002756:Cholagogues and Choleretics; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D017294:Ondansetron; D013395:Sucrose; D002766:Cholecystokinin