Cholecystokinin-induced satiety is mediated through interdependent cooperation of CCK-A and 5-HT3 receptors.
Recent evidence supports a role for the serotonin-3 (5-HT3) receptors in the modulation of cholecystokinin (CCK)-induced satiation. Likewise, 5-HT's anorectic response has been linked to recruitment of peripheral CCK-A receptors. Evidence to date, however, does not elucidate whether there is a concomitant interaction between CCK-A and 5-HT3 receptors or whether each receptor functions independently in the negative feedback control of food intake elicited by CCK. In the present study, we used selective receptor antagonists to investigate the roles of CCK-A and 5-HT3 receptors in CCK-induced satiation. Intraperitoneal administration of CCK-8 reduced 30-min 15% sucrose intake in a dose-responsive manner. Prior treatment with ondansetron (1.0 mg/kg ip), a highly selective 5-HT3 receptor antagonist, attenuated CCK-induced suppression of food intake in a dose-responsive manner. Pretreatment with lorglumide (1.0 mg/kg ip), a selective CCK-A receptor antagonist, reversed CCK-induced inhibition of sucrose intake. Finally, simultaneous blockade of CCK-A and 5-HT3 receptors by lorglumide and ondansetron, as well as concomitant administration of the two antagonists with CCK, produced a significant synergistic increase in sucrose intake compared with intakes after administration of saline, CCK, or either antagonist alone. These findings support evidence that CCK-A and 5-HT3 receptors cooperate interdependently in control of short-term food intake. Most likely, this interconnection exists through a feed-forward parallel model arising from CCK-A and 5-HT3 receptors, where activation of one system engages the other to intensify the overall satiety signal.
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, 126 South Henderson, University Park, PA 16802-6504, USA. mrh212@psu.edu
Matthew R
MR
Hayes
David M
DM
Savastano
Mihai
M
Covasa
D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000502:physiology*; D012528:Satiety Response / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology
D006727:Hormone Antagonists; D043886:Receptor, Cholecystokinin A; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017294:Ondansetron; D002766:Cholecystokinin; D011377:Proglumide; C048181:lorglumide