CALL FOR PAPERS Physiological Regulation of Appetite Serotonin-type 3 receptors mediate intestinal Polycose- and glucose-induced suppression of intake

Savastano, David M., Melissa Carelle, and Mihai Covasa. Serotonin-type 3 receptors mediate intestinal Polycoseand glucoseinduced suppression of intake. Am J Physiol Regul Integr Comp Physiol 288: R1499–R1508, 2005. First published February 17, 2005; doi:10.1152/ajpregu.00745.2004.—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, glucoseinduced 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.