As part of our studies to elucidate the mechanism of action of BRS-3 agonists, we have preliminary data that BRS-3 agonists increase metabolic rate via stimulating brown adipose tissue. These studies are being confirmed and expanded upon. We are also investigating the role fo BRS-3 in blood pressure control. In order to study the specific cells, sites, tissues, and transmitters by which BRS-3 acts, we are generating the following tools: 1) a conditional knockout floxed Brs3 mouse, 2) a knockin mouse with Cre recombinase driven by Brs3, and 3) a BAC transgenic mouse with Brs3 driving GFP expression. The long-term investment required to generate and validate these tools is expected to yield great rewards in future years. We are collaborating with Merck, using selective BRS-3 compounds (particularly the agonists MK-5046 and MK-7255). 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 to publication.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2013
Total Cost
$336,109
Indirect Cost
City
State
Country
Zip Code
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
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