Pharmacological characterization of a selective agonist for bombesin receptor subtype-3 |
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Authors: | Li Zhang Hans-Peter Nothacker Laura M. Bohn Olivier Civelli |
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Affiliation: | a Department of Pharmacology, University of California, Irvine, CA 92697, USA b Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA c Department of Pharmacology, Ohio State University, Columbus, OH 43210, USA d Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458, USA |
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Abstract: | Bombesin receptor subtype-3 (BRS-3) is an orphan G protein-coupled receptor in the bombesin receptor family that still awaits identification of its natural ligand. BRS-3 deficient mice develop a mild late-onset obesity with metabolic defects, implicating BRS-3 plays a role in feeding and metabolism. We describe here the pharmacological characterization of a synthetic compound, 16a, which serves as a potent agonist for BRS-3. This compound is selective for BRS-3 as it does not activate neuromedin B or gastrin-releasing peptide receptors, two most closely related bombesin receptors, as well as a series of other GPCRs. We assessed the receptor trafficking of BRS-3 and found that compound 16a promoted β-arrestin translocation to the cell membrane. Neither central nor peripheral administration of compound 16a affects locomotor activity in mice. Therefore compound 16a is a potential tool to study the function of the BRS-3 system in vitro and possibly in vivo. |
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Keywords: | Bombesin receptor subtype-3 Agonist Calcium mobilization Receptor trafficking β-Arrestin |
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