Pharmacological characterization of a selective agonist for bombesin receptor subtype-3.
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.
Zhang
Li
L
Department of Pharmacology, University of California, Irvine, CA 92697, USA.
Nothacker
Hans-Peter
HP
Wang
Zhiwei
Z
Bohn
Laura M
LM
Civelli
Olivier
O
D000818:Animals; D019390:Arrestins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D018004:Receptors, Bombesin / Q000819:agonists*; D000071557:beta-Arrestins
D019390:Arrestins; D007211:Indoles; C542913:N1-(2-phenylethyl)-(2R)-2-(((1S)-1-(benzylcarboxamido)ethyl)carboxamido)-3-(1H-3-indolyl)propanamide; D018004:Receptors, Bombesin; D000071557:beta-Arrestins; C107120:bombesin receptor subtype 3