Loss of bombesin-induced feeding suppression in gastrin-releasing peptide receptor-deficient mice.
The gastrin-releasing peptide receptor (GRP-R) is one of three members of the mammalian bombesin subfamily of seven-transmembrane G protein-coupled receptors that mediate diverse biological responses including secretion, neuromodulation, chemotaxis, and growth. The X chromosome-linked GRP-R gene is expressed widely during embryonic development and predominantly in gastrointestinal, neuronal, and neuroendocrine systems in the adult. Surprisingly, gene-targeted mice lacking a functional GRP-R gene develop and reproduce normally and show no gross phenotypic abnormalities. However, peripheral administration of bombesin at dosages up to 32 nmol/kg to such mice had no effect on the suppression of glucose intake, whereas normal mice showed a dose-dependent suppression of glucose intake. These data suggest that selective agonists for the GRP-R may be useful in inducing satiety.
Hampton
L L
LL
Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
Ladenheim
E E
EE
Akeson
M
M
Way
J M
JM
Weber
H C
HC
Sutliff
V E
VE
Jensen
R T
RT
Wine
L J
LJ
Arnheiter
H
H
Battey
J F
JF
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D051379:Mice; D008817:Mice, Mutant Strains; D010179:Pancreas / Q000187:drug effects; D018004:Receptors, Bombesin / Q000819:agonists / Q000172:deficiency* / Q000235:genetics; D012527:Satiation / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology
D018004:Receptors, Bombesin; D002217:Carbachol; D000681:Amylases; D012844:Sincalide; D001839:Bombesin