Bombesin, but not amylin, blocks the orexigenic effect of peripheral ghrelin.
The interaction between ghrelin and bombesin or amylin administered intraperitoneally on food intake and brain neuronal activity was assessed by Fos-like immunoreactivity (FLI) in nonfasted rats. Ghrelin (13 microg/kg ip) increased food intake compared with the vehicle group when measured at 30 min (g/kg: 3.66 +/- 0.80 vs. 1.68 +/- 0.42, P < 0.0087). Bombesin (8 microg/kg) injected intraperitoneally with ghrelin (13 microg/kg) blocked the orexigenic effect of ghrelin (1.18 +/- 0.41 g/kg, P < 0.0002). Bombesin alone (4 and 8 microg/kg ip) exerted a dose-related nonsignificant reduction of food intake (g/kg: 1.08 +/- 0.44, P > 0.45 and 0.55 +/- 0.34, P > 0.16, respectively). By contrast, ghrelin-induced stimulation of food intake (g/kg: 3.96 +/- 0.56 g/kg vs. vehicle 0.82 +/- 0.59, P < 0.004) was not altered by amylin (1 and 5 microg/kg ip) (g/kg: 4.37 +/- 1.12, P > 0.69, and 3.01 +/- 0.78, respectively, P > 0.37). Ghrelin increased the number of FLI-positive neurons/section in the arcuate nucleus (ARC) compared with vehicle (median: 42 vs. 19, P < 0.008). Bombesin alone (4 and 8 microg/kg ip) did not induce FLI neurons in the paraventricular nucleus of the hypothalamus (PVN) and coadministered with ghrelin did not alter ghrelin-induced FLI in the ARC. However, bombesin (8 microg/kg) with ghrelin significantly increased neuronal activity in the PVN approximately threefold compared with vehicle and approximately 1.5-fold compared with the ghrelin group. Bombesin (8 microg/kg) with ghrelin injected intraperitoneally induced Fos expression in 22.4 +/- 0.8% of CRF-immunoreactive neurons in the PVN. These results suggest that peripheral bombesin, unlike amylin, inhibits peripheral ghrelin induced food intake and enhances activation of CRF neurons in the PVN.
Kobelt
Peter
P
Department of Medicine, Charité-Universitätsmedizin Berlin, Germany.
Goebel
Miriam
M
Stengel
Andreas
A
Schmidtmann
Marco
M
van der Voort
Ivo R
IR
Tebbe
Johannes J
JJ
Veh
Rüdiger W
RW
Klapp
Burghard F
BF
Wiedenmann
Bertram
B
Wang
Lixin
L
Taché
Yvette
Y
Mönnikes
Hubert
H
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001839:Bombesin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D054439:Ghrelin; D007274:Injections, Intraperitoneal; D058228:Islet Amyloid Polypeptide; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D036361:Peptide Hormones / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000682:Amyloid; D000897:Anti-Ulcer Agents; D054439:Ghrelin; D058228:Islet Amyloid Polypeptide; D018377:Neurotransmitter Agents; D036361:Peptide Hormones; D016760:Proto-Oncogene Proteins c-fos; D001839:Bombesin