Functional properties of two bombesin-like peptide receptors revealed by the analysis of mice lacking neuromedin B receptor

The neuromedin B-preferring receptor (NMB-R) is one of the members of the b ombesin (BN)-like peptide receptor subfamily in mammals. Previously, we hav e generated and characterized mice with targeted disruption of the two othe r BN-like peptide receptors, bombesin receptor subtype-3 (BRS-3) and gastri n-releasing peptide-preferring receptor (GRP-R). Here we describe the gener ation and analysis of NMB-R-deficient mice to investigate how NMB-R differs from BRS-3 and GRP-R. Compensation for NMB-R deficiency by overexpression of GRP-R and/or BRS-3 was not detected. Although the hypothermic effect of NMB was reduced by 50% in NMB-R-deficient mice, the effect of GRP infusion was comparable to the wild-type mice. In contrast, fundic smooth muscle con traction on stimulation with NMB or GRP was normal in NMB-R-deficient mice. Administration of GRP but not NMB suppressed glucose intake in both normal and NMB-R-deficient mice. These results suggest that the NMB-R has an esse ntial role in thermoregulation, but not for smooth muscle contraction of th e fundus or for the suppression of feeding behavior. In addition, the behav ioral phenotypes of GRP-R-deficient mice were not observed in NMB-R-deficie nt mice. These data show that the functions of NMB-R and GRP-R are distinct , with only partial overlap.