Characterization And Pharmacology Of Receptors For Gastrointestinal Peptides

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

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Abstract

During the year the receptor pharmacology and molecular pharmacology of primarily of the bombesin receptor family (GRPR, NMBR, BRS-3) was investigated. During this year a study elaborating the pharmacology, characterization and synthesis of the first radiolabeled antagonist that interacts with high affinity with the bombesin related orphan receptor BRS3 was published. This ligand has very high affinity and selectivity for this receptor, which is receiving increasing attention for its roles in regulating glucose/insulin homeostasis, and fat metabolism and thus playing a role in diabetes and obesity. It also has numerous CNS effects that are receiving increased attention including related to satiety, energy metabolism, behavioral changes, and body temperature control. This ligand should prove particularly useful for helping to defining the role of this receptor in these different processes. Also, BRS-3 similar to the other bombesin receptor family members is reported to be overexpressed by a number of human tumors. This year a study of BRS-3 in lung cancer cell lines was completed because activation of the other bombesin receptor (GRPR,NMBR) have marked growth effects on these tumors, but the role of BRS-3 is not well defined. This study showed BRS3 is even more frequent that GRPR or NMBR in these cancers, they are biologically active in the tumor cells affecting intracellular signaling cascades and tumor growth, and they could prove to be an important antii tumor growth target in these cancers. In addition, a general review of the role of bombesin receptor family as well as other neuropeptide G protein coupled receptor families functioning as an oncotarget was published, based on both our studies as well as others.