Physiology and Pharmacology of BRS-3 (Bombesin Receptor Subtype-3)

Reitman, Marc L.

Abstract

I arrived at the NIH during this year and much of my effort has been devoted to setting up my laboratory. We have established a colony of BRS-3 knockout mice. A conditional floxed knockout does not yet exist for BRS-3 and we are in the process of making such a mouse. We also plan to generate a transgenic mouse with Cre recombinase driven by BRS-3. An MTA that enables us to get BRS-3 compounds (MK-5046, MK-7255, and Bantag-1) from Merck has been created. The mouse physiology capabilities needed are also being established, including the ability to measure metabolic rate at thermoneutrality and a telemetry system for continuous body temperature monitoring. Additionally, work on BRS-3 that I was involved with at Merck Research Laboratories prior to my arrival at NIDDK continues to be guided through the publication process.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIADK075057-01
• Application #: 8349965
• Support Year: 1
• Fiscal Year: 2011
• Total Cost: $916,107

Institution

• Name: National Institute of Diabetes and Digestive and Kidney Diseases

Publications

Xiao, Cuiying; Piñol, Ramón A; Carlin, Jesse Lea et al. (2018) Corrigendum to ""Bombesin-like receptor 3 (Brs3) expression in glutamatergic, but not GABAergic, neurons is required for regulation of energy metabolism"" [Mol Metabol 6 (2017) 1540-1550]. Mol Metab 9:220

Piñol, Ramón A; Zahler, Sebastian H; Li, Chia et al. (2018) Brs3 neurons in the mouse dorsomedial hypothalamus regulate body temperature, energy expenditure, and heart rate, but not food intake. Nat Neurosci 21:1530-1540

Lateef, Dalya M; Xiao, Cuiying; Brychta, Robert J et al. (2016) Bombesin-like receptor 3 regulates blood pressure and heart rate via a central sympathetic mechanism. Am J Physiol Heart Circ Physiol 310:H891-8

Xiao, Cuiying; Reitman, Marc L (2016) Bombesin-Like Receptor 3: Physiology of a Functional Orphan. Trends Endocrinol Metab 27:603-605

Lateef, Dalya M; Xiao, Cuiying; Reitman, Marc L (2015) Search for an Endogenous Bombesin-Like Receptor 3 (BRS-3) Ligand Using Parabiotic Mice. PLoS One 10:e0142637

Lateef, Dalya M; Abreu-Vieira, Gustavo; Xiao, Cuiying et al. (2014) Regulation of body temperature and brown adipose tissue thermogenesis by bombesin receptor subtype-3. Am J Physiol Endocrinol Metab 306:E681-7

Hatoum, Ida J; Greenawalt, Danielle M; Cotsapas, Chris et al. (2013) Weight loss after gastric bypass is associated with a variant at 15q26.1. Am J Hum Genet 92:827-34

Moreno, Paola; Mantey, Samuel A; Nuche-Berenguer, Bernardo et al. (2013) Comparative pharmacology of bombesin receptor subtype-3, nonpeptide agonist MK-5046, a universal peptide agonist, and peptide antagonist Bantag-1 for human bombesin receptors. J Pharmacol Exp Ther 347:100-16

Reitman, Marc L (2013) FGF21 mimetic shows therapeutic promise. Cell Metab 18:307-9

Chobanian, Harry R; Guo, Yan; Liu, Ping et al. (2012) The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization. Bioorg Med Chem 20:2845-9