CCK inhibits the orexigenic effect of peripheral ghrelin.
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.
Kobelt
Peter
P
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.
Tebbe
Johannes J
JJ
Tjandra
Ines
I
Stengel
Andreas
A
Bae
Hi-Gung
HG
Andresen
Viola
V
van der Voort
Ivo R
IR
Veh
Rüdiger W
RW
Werner
Christoph R
CR
Klapp
Burghard F
BF
Wiedenmann
Bertram
B
Wang
Lixin
L
Taché
Yvette
Y
Mönnikes
Hubert
H
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
C090019:8-sulfocholecystokinin octapeptide; D054439:Ghrelin; D036361:Peptide Hormones; D016760:Proto-Oncogene Proteins c-fos; D002766:Cholecystokinin; D012844:Sincalide