title: Bombesin, but not amylin, blocks the orexigenic effect of peripheral ghrelin.
abstract: 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.
authors.affiliation: Department of Medicine, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kobelt
authors.forename: Miriam
authors.initials: M
authors.lastname: Goebel
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
authors.forename: Marco
authors.initials: M
authors.lastname: Schmidtmann
authors.forename: Ivo R
authors.initials: IR
authors.lastname: van der Voort
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Tebbe
authors.forename: Rüdiger W
authors.initials: RW
authors.lastname: Veh
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: 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
chemical_list: 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