Serotonin-type 3 receptors mediate intestinal Polycose- and glucose-induced suppression of intake.
Ondansetron, a selective serotonin-type 3 (5-HT(3)) receptor antagonist, was used to test the hypothesis that duodenal infusion of isosmotic solutions of Polycose or its hydrolytic product glucose suppressed intake through 5-HT(3) receptors. Polycose suppressed sucrose intake across both concentrations infused (132 mM, 7.6 +/- 0.6 ml; 263 mM, 2.3 +/- 0.5 ml), compared with intake under control conditions (12.6 +/- 0.3 ml, P <0.001). Pretreatment with 1.0 mg/kg ondansetron attenuated reduction of sucrose intake induced only by the highest concentration of Polycose (4.6 +/- 0.8 ml, P = 0.004). Dose-response testing revealed that suppression of food intake by 263 mM Polycose was equally attenuated by ondansetron administered at 1.0, 2.0, and 5.0 mg/kg but not when given at 0.125, 0.25, and 0.5 mg/kg. Acarbose, an alpha-glucosidase inhibitor, attenuated Polycose-induced suppression of food intake, and pretreatment with 1.0 mg/kg ondansetron had no further effect. Suppression of intake after 990 mM glucose but not mannitol infusion was attenuated by pretreatment with 1.0 mg/kg ondansetron. The competitive SGLT(1) inhibitor, phloridzin, had no effect on 60-min 990 mM glucose-induced suppression of intake or the ability of ondansetron to attenuate this suppression of intake. Conversely, glucose-induced suppression of intake was attenuated by phloridzin at earlier time points and further attenuated when rats were pretreated with 1.0 mg/kg ondansetron. Ondansetron administration alone had no effect on intake at any dose tested. We conclude that 5-HT(3) receptors participate in the inhibition of food intake by intraduodenal infusion of carbohydrate solutions through a posthydrolytic, preabsorptive mechanism.
Savastano
David M
DM
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, 126 South Henderson, University Park, PA 16802, USA. dms493@psu.edu
Carelle
Melissa
M
Covasa
Mihai
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004386:Duodenum; D004435:Eating / Q000187:drug effects*; D005936:Glucans / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006868:Hydrolysis; D007422:Intestines / Q000187:drug effects / Q000502:physiology*; D007441:Intubation, Gastrointestinal; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology
D005936:Glucans; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017294:Ondansetron; D010695:Phlorhizin; D005947:Glucose