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Physiological Regulation of Appetite

Serotonin-type 3 receptors mediate intestinal Polycose- and glucose-induced suppression of intake

Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, Pennsylvania

Submitted 3 November 2004 ; accepted in final form 13 February 2005

Ondansetron, a selective serotonin-type 3 (5-HT₃) 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-HT₃ 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 -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 SGLT₁ 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-HT₃ receptors participate in the inhibition of food intake by intraduodenal infusion of carbohydrate solutions through a posthydrolytic, preabsorptive mechanism.

nutrient absorption; food intake; satiation

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