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-HT 3 ) receptor antagonist, was used to test...

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Veröffentlicht in:American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2005-06, Vol.288 (6), p.R1499-R1508
Hauptverfasser: Savastano, David M, Carelle, Melissa, Covasa, Mihai
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container_end_page R1508
container_issue 6
container_start_page R1499
container_title American journal of physiology. Regulatory, integrative and comparative physiology
container_volume 288
creator Savastano, David M
Carelle, Melissa
Covasa, Mihai
description 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-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
doi_str_mv 10.1152/ajpregu.00745.2004
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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 &lt;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 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. nutrient absorption; food intake; satiation Address for reprint requests and other correspondence: D. M. 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Regulatory, integrative and comparative physiology</title><addtitle>Am J Physiol Regul Integr Comp Physiol</addtitle><description>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-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 &lt;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 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. nutrient absorption; food intake; satiation Address for reprint requests and other correspondence: D. M. Savastano, Dept. of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State Univ., 126 South Henderson, University Park, PA 16802 (E-mail: dms493{at}psu.edu )</description><subject>Animals</subject><subject>Dose-Response Relationship, Drug</subject><subject>Duodenum</subject><subject>Eating - drug effects</subject><subject>Glucans - administration &amp; dosage</subject><subject>Glucans - pharmacokinetics</subject><subject>Glucans - pharmacology</subject><subject>Glucose - administration &amp; dosage</subject><subject>Glucose - pharmacokinetics</subject><subject>Glucose - pharmacology</subject><subject>Hydrolysis</subject><subject>Intestines - drug effects</subject><subject>Intestines - physiology</subject><subject>Intubation, Gastrointestinal</subject><subject>Male</subject><subject>Ondansetron - pharmacology</subject><subject>Phlorhizin - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Serotonin, 5-HT3 - drug effects</subject><subject>Serotonin Antagonists - pharmacology</subject><issn>0363-6119</issn><issn>1522-1490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUtr3DAURkVpaCZp_0AXRavuPNHDtuTuSmgeEEjIYy000vWMphrLlWwa__toHmmzyeoi7nc-LkcIfaVkTmnFzvS6j7Ac54SIspozQsoPaJYXrKBlQz6iGeE1L2pKm2N0ktKa5AQv-Sd0TCtBJW_IDOkHiGEIneuKYeoBcxzBQD-EmPAGrNMDYNcNkAbXaY_vgp9MSFBg3Vm89OPu4To7GrA4jX2-KCUXOhzaLad_w2d01Gqf4MthnqKni1-P51fFze3l9fnPm8KUvBoKyWXDDWeU2pZXDWs1VLUBzZlYcFtKVoKmGoxdCKYFa1kr69q2VnAmaSkoP0Xf9719DH_GfLDauGTAe91BGJOqhaSCEJaDbB80MaQUoVV9dBsdJ0WJ2opVB7FqJ1ZtxWbo26F9XGQv_5GDyRyY7wMrt1z9dRFUv5qyCR-W079CJqWq1X3-niYDP94HLkbvH-F5eCXfgKrPgl4AHIqdOQ</recordid><startdate>20050601</startdate><enddate>20050601</enddate><creator>Savastano, David M</creator><creator>Carelle, Melissa</creator><creator>Covasa, Mihai</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20050601</creationdate><title>Serotonin-type 3 receptors mediate intestinal Polycose- and glucose-induced suppression of intake</title><author>Savastano, David M ; Carelle, Melissa ; Covasa, Mihai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-83893c3211df3592fae56cea327b3d4824ea1aecdb72a72f2f866dfd732814713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Dose-Response Relationship, Drug</topic><topic>Duodenum</topic><topic>Eating - drug effects</topic><topic>Glucans - administration &amp; dosage</topic><topic>Glucans - pharmacokinetics</topic><topic>Glucans - pharmacology</topic><topic>Glucose - administration &amp; dosage</topic><topic>Glucose - pharmacokinetics</topic><topic>Glucose - pharmacology</topic><topic>Hydrolysis</topic><topic>Intestines - drug effects</topic><topic>Intestines - physiology</topic><topic>Intubation, Gastrointestinal</topic><topic>Male</topic><topic>Ondansetron - pharmacology</topic><topic>Phlorhizin - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Serotonin, 5-HT3 - drug effects</topic><topic>Serotonin Antagonists - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Savastano, David M</creatorcontrib><creatorcontrib>Carelle, Melissa</creatorcontrib><creatorcontrib>Covasa, Mihai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology. 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Regulatory, integrative and comparative physiology</jtitle><addtitle>Am J Physiol Regul Integr Comp Physiol</addtitle><date>2005-06-01</date><risdate>2005</risdate><volume>288</volume><issue>6</issue><spage>R1499</spage><epage>R1508</epage><pages>R1499-R1508</pages><issn>0363-6119</issn><eissn>1522-1490</eissn><abstract>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-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 &lt;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 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. nutrient absorption; food intake; satiation Address for reprint requests and other correspondence: D. M. Savastano, Dept. of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State Univ., 126 South Henderson, University Park, PA 16802 (E-mail: dms493{at}psu.edu )</abstract><cop>United States</cop><pmid>15718390</pmid><doi>10.1152/ajpregu.00745.2004</doi><oa>free_for_read</oa></addata></record>
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source MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects Animals
Dose-Response Relationship, Drug
Duodenum
Eating - drug effects
Glucans - administration & dosage
Glucans - pharmacokinetics
Glucans - pharmacology
Glucose - administration & dosage
Glucose - pharmacokinetics
Glucose - pharmacology
Hydrolysis
Intestines - drug effects
Intestines - physiology
Intubation, Gastrointestinal
Male
Ondansetron - pharmacology
Phlorhizin - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Serotonin, 5-HT3 - drug effects
Serotonin Antagonists - pharmacology
title Serotonin-type 3 receptors mediate intestinal Polycose- and glucose-induced suppression of intake
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