Desensitization of neuromedin B receptors (NMB-R) on native and NMB-R-transfected cells involves down-regulation and internalization.

Bombesin Receptor Family Activation and CNS/Neural Tumors: Review of Evidence Supporting Possible Role for Novel Targeted Therapy

“…Detailed stoichiometric studies ( 150 , 151 ) of the ability of NMB to occupy the NMBR and stimulate cellular signaling cascades on C6-glioma cells compared to coupling of human NMBR in normal cells ( Figure 1 ) demonstrated identical coupling for all the signaling cascades. Similarly in these studies, the NMBR in C6-glioma cells underwent agonist-induced internalization, downregulation, and desensitization in a similar manner to NMBRs on normal cells ( 12 , 96 – 98 , 110 , 111 , 151 ). In human neuroblastoma cell lines, BnR agonists ( via GRPR) stimulated phospholipase C activation ( 188 , 195 , 196 ), which was by a pertussis toxin-sensitive G protein mechanism and was Ca 2+ and PKC independent ( 195 ).…”

“…Post receptor activation, each of the Bn receptor subtypes undergo a number of processes, similar to other GPCRs, including receptor phosphorylation, receptor internalization, downregulation, and desensitization (12,47,93,97,98,(108)(109)(110)(111)(112)(113).…”

Glycosylation of Bombesin Receptors: Characterization, Effect on Binding, and G-Protein Coupling

“…Although receptors for NMB and GRP share considerable homology (Wada et al, 1991) and similar pharmacological properties, including high-affinity binding for bombesin (Wang et al, 1993) and being coupled to phospholipase C (Benya et al, 1992(Benya et al, ,1994, the results in the present study disclose several structural differences between these two bombesin receptor types related to glycosylation. Both classes of receptors showed distinct relative molecular weights after cross-linking on SDS-PAGE (Mr = 63 000 and Mr = 82 000 for NMB-R and GRP-R transfected cells, respectively).…”

“…NMB receptors were investigated using this methodology in both the rat glioblastoma C-6 cells and the NMB-R from rat esophageal muscularis mucosa transfected into BALB-3T3 cells (Benya et al, 1992). These NMB receptor cell types were selected because recent studies demonstrate that each is pharmacologically similar to NMB receptors on esophageal mucosa and that activation of each alters cell function in a similar manner, including increasing [Ca2+]j and inositol phosphates and causing receptor downregulation, internalization, and desensitization (Benya et al, 1992(Benya et al, ,1994. These results were compared with those for the mouse GRP receptor, which was also transfected into these cells and is glycosylated to an extent identical to that in native mouse 3T3 cells and which has been shown to behave in a pharmacologically similar fashion to the native murine GRP receptor in Swiss 3T3 cells (Benya et al, 1994).…”

“…These NMB receptor cell types were selected because recent studies demonstrate that each is pharmacologically similar to NMB receptors on esophageal mucosa and that activation of each alters cell function in a similar manner, including increasing [Ca2+]j and inositol phosphates and causing receptor downregulation, internalization, and desensitization (Benya et al, 1992(Benya et al, ,1994. These results were compared with those for the mouse GRP receptor, which was also transfected into these cells and is glycosylated to an extent identical to that in native mouse 3T3 cells and which has been shown to behave in a pharmacologically similar fashion to the native murine GRP receptor in Swiss 3T3 cells (Benya et al, 1994). The present studies show that the NMB-R ligand, [125I]-(D-Tyr°)NMB, is covalently linked to a single polypeptide, Mr = 63 000 (when corrected for the relative molecular weight of [125I] -(D-Tyr0)-NMB), in membranes from both C-6 and NMB-R transfected cells.…”