title: CCK inhibits the orexigenic effect of peripheral ghrelin.
abstract: CCK and ghrelin exert antagonistic effects on ingestive behavior. The aim of the present study was to investigate the interaction between ghrelin and CCK administered peripherally on food intake and neuronal activity in specific hypothalamic and brain stem nuclei, as assessed by c-Fos-like immunoreactivity (c-FLI) in nonfasted rats. Ghrelin (13 microg/kg body wt) injected intraperitoneally significantly increased the cumulative food intake when measured at 30 min and 1 h after injection, compared with the vehicle group (2.9 +/- 1.0 g/kg body wt vs. 1.2 +/- 0.5 g/kg body wt, P < 0.028). Sulfated CCK octapeptide (CCK-8S) (2 or 25 microg/kg body wt) injected simultaneously blocked the orexigenic effect of ghrelin (0.22 +/- 0.13 g/kg body wt, P < 0.001 and 0.33 +/- 0.23 g/kg body wt, P < 0.0008), while injected alone, both doses of CCK-8S exerted a nonsignificant trend to reduce food intake. Ghrelin (13 microg/kg body wt ip) markedly increased the number of c-FLI-positive neurons per section in the arcuate nucleus (ARC) compared with vehicle (median: 31.35 vs. 9.86, P < 0.0001). CCK-8S (2 or 25 microg/kg body wt ip) had no effect on neuronal activity in the ARC, as assessed by c-FLI (median: 5.33 and 11.21 cells per section), but blocked the ghrelin-induced increase of c-fos expression in this area when both peptides were administered simultaneously (median: 13.33 and 12.86 cells per section, respectively). Ghrelin at this dose had no effect on CCK-induced stimulation of c-fos expression in the paraventricular nucleus of the hypothalamus and the nucleus of the solitary tract. These results suggest that CCK abolishes ghrelin-induced food intake through dampening increased ARC neuronal activity.
authors.affiliation: Department of Medicine, Division of Hepatology and Gastroenterology, Charité, Medical Faculty of Freie Universität and Humboldt-Universität at Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kobelt
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Tebbe
authors.forename: Ines
authors.initials: I
authors.lastname: Tjandra
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
authors.forename: Hi-Gung
authors.initials: HG
authors.lastname: Bae
authors.forename: Viola
authors.initials: V
authors.lastname: Andresen
authors.forename: Ivo R
authors.initials: IR
authors.lastname: van der Voort
authors.forename: Rüdiger W
authors.initials: RW
authors.lastname: Veh
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Werner
authors.forename: Burghard F
authors.initials: BF
authors.lastname: Klapp
authors.forename: Bertram
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
authors.forename: Hubert
authors.initials: H
authors.lastname: Mönnikes
mesh_terms: D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D002766:Cholecystokinin / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D054439:Ghrelin; D007274:Injections, Intraperitoneal; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D036361:Peptide Hormones / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017552:Solitary Nucleus / Q000378:metabolism
chemical_list: C090019:8-sulfocholecystokinin octapeptide; D054439:Ghrelin; D036361:Peptide Hormones; D016760:Proto-Oncogene Proteins c-fos; D002766:Cholecystokinin; D012844:Sincalide