Get access

Anatomical characterization of bombesin receptor subtype-3 mRNA expression in the rodent central nervous system

Authors

  • Li Zhang,

    1. Department of Pharmacology, University of California Irvine, Irvine, California 92697
    2. Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, 92697
    Current affiliation:
    1. Janssen Research and Development, LLC, 3210 Merryfield Row, San Diego, CA 92121
    Search for more papers by this author
  • Gregory S. Parks,

    1. Department of Pharmacology, University of California Irvine, Irvine, California 92697
    2. Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, 92697
    Search for more papers by this author
  • Zhiwei Wang,

    1. Department of Pharmacology, University of California Irvine, Irvine, California 92697
    Search for more papers by this author
  • Lien Wang,

    1. Department of Pharmacology, University of California Irvine, Irvine, California 92697
    Search for more papers by this author
  • Michelle Lew,

    1. Department of Pharmacology, University of California Irvine, Irvine, California 92697
    Search for more papers by this author
  • Olivier Civelli

    Corresponding author
    1. Department of Pharmacology, University of California Irvine, Irvine, California 92697
    2. Department of Developmental and Cell Biology, University of California Irvine, Irvine, California, 92697
    3. Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California, 92697
    • University of California Irvine, 369 Med Surge II, Irvine, CA 92697
    Search for more papers by this author

Abstract

Bombesin receptor subtype-3 (BRS-3) is an orphan G-protein-coupled receptor (GPCR) involved in the regulation of energy homeostasis. Mice deficient in BRS-3 develop late-onset mild obesity with metabolic defects, while synthetic agonists activating BRS-3 show antiobesity profiles by inhibiting food intake and increasing metabolic rate in rodent models. The molecular mechanisms and the neural circuits responsible for these effects, however, remain elusive and demand better characterization. We report here a comprehensive mapping of BRS-3 mRNA in the rat and mouse brain through in situ hybridization. Furthermore, to investigate the neurochemical characteristics of the BRS-3-expressing neurons, double in situ hybridization was performed to determine whether BRS-3 colocalizes with other neurotransmitters or neuropeptides. Many, but not all, of the BRS-3-expressing neurons were found to be glutamatergic, while few were found to be cholinergic or GABAergic. BRS-3-containing neurons do not express some of the well-characterized neuropeptides, such as neuropeptide Y (NPY), proopiomelanocortin (POMC), orexin/hypocretin, melanin-concentrating hormone (MCH), thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), and kisspeptin. Interestingly, BRS-3 mRNA was found to partially colocalize with corticotropin-releasing factor (CRF) and growth hormone-releasing hormone (GHRH), suggesting novel interactions of BRS-3 with stress- and growth-related endocrine systems. Our study provides important information for evaluating BRS-3 as a potential therapeutic target for the treatment of obesity. J. Comp. Neurol. 521:1020–1039, 2013. © 2012 Wiley Periodicals, Inc.

Ancillary