Disruptions in feeding and body weight control in gastrin-releasing peptide receptor deficient mice.
Bombesin (BN) interacts with two mammalian receptor subtypes termed gastrin-releasing peptide (GRP)-preferring (GRP-R) and neuromedin B (NMB)-preferring (NMB-R) that may mediate the satiety action of BN. We examined the feeding behavior of mice that were deficient in the GRP-R (GRP-R KO) to assess the overall contribution of this receptor subtype in the feeding actions of BN-related peptides. GRP-R KO mice failed to suppress glucose intake in response to systemically administered BN and GRP(18-27), whereas both peptides elicited a potent reduction of intake in wild-type (WT) mice. Neither GRP-R KO nor WT mice suppressed glucose intake following NMB administration. Unlike the impaired responses to BN-like peptides, the feeding inhibitory action of cholecystokinin was enhanced in GRP-R KO mice. Consistent with behavioral results, GRP-R KO mice also exhibited a reduction in c-Fos immunoreactivity in the nucleus of the solitary tract (NTS) and paraventricular nucleus (PVN) following peripheral administration of BN. An evaluation of meal patterns showed that GRP-R KO mice ate significantly more at each meal than WT mice, although total 24 h food consumption was equivalent. A long-term analysis of body weight revealed a significant elevation in GRP-R KO mice compared with WT littermates beginning at 45 weeks of age. These data suggest that the GRP-R mediates the feeding effects of BN-like peptides and participates in the termination of meals in mice.
Ladenheim
E E
EE
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. laden@jhmi.edu
Hampton
L L
LL
Whitney
A C
AC
White
W O
WO
Battey
J F
JF
Moran
T H
TH
D000818:Animals; D001345:Autoradiography; D001835:Body Weight / Q000187:drug effects; D001839:Bombesin / Q000378:metabolism / Q000494:pharmacology; D001923:Brain Chemistry; D002766:Cholecystokinin / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D018004:Receptors, Bombesin / Q000172:deficiency* / Q000235:genetics; D012528:Satiety Response / Q000187:drug effects*
D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D018004:Receptors, Bombesin; C040794:neuromedin C; D015287:Neurokinin B; C038393:neuromedin B; D002766:Cholecystokinin; D001839:Bombesin