Pharmacological characterization of a selective agonist for bombesin receptor subtype-3

Biochem Biophys Res Commun. 2009 Sep 18;387(2):283-8. doi: 10.1016/j.bbrc.2009.07.006. Epub 2009 Jul 4.

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 beta-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arrestins / metabolism
  • Cell Membrane / metabolism
  • Humans
  • Indoles / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Protein Transport / drug effects
  • Rats
  • Receptors, Bombesin / agonists*
  • beta-Arrestins

Substances

  • Arrestins
  • Indoles
  • N1-(2-phenylethyl)-(2R)-2-(((1S)-1-(benzylcarboxamido)ethyl)carboxamido)-3-(1H-3-indolyl)propanamide
  • Receptors, Bombesin
  • beta-Arrestins
  • bombesin receptor subtype 3