Protocol

G Protein-Coupled Receptors in Drug Discovery

Volume 1335 of the series Methods in Molecular Biology pp 205-221

Virus-Mediated Expression of DREADDs for In Vivo Metabolic Studies

  • Mario RossiAffiliated withMolecular Signaling Section, Laboratory of Bioorganic Chemistry, NIH-NIDDK
  • , Zhenzhong CuiAffiliated withMolecular Signaling Section, Laboratory of Bioorganic Chemistry, NIH-NIDDK
  • , Ken-ichiro NakajimaAffiliated withMolecular Signaling Section, Laboratory of Bioorganic Chemistry, NIH-NIDDK
  • , Jianxin HuAffiliated withMolecular Signaling Section, Laboratory of Bioorganic Chemistry, NIH-NIDDK
  • , Lu ZhuAffiliated withMolecular Signaling Section, Laboratory of Bioorganic Chemistry, NIH-NIDDK
  • , Jürgen WessAffiliated withMolecular Signaling Section, Laboratory of Bioorganic Chemistry, NIH-NIDDK Email author 

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Abstract

During the past few years, CNO-sensitive designer G protein-coupled receptors (GPCRs) known as DREADDs (designer receptors exclusively activated by designer drugs) have emerged as powerful new tools for the study of GPCR physiology. In this chapter, we present protocols employing adeno-associated viruses (AAVs) to express a Gq-coupled DREADD (Dq) in two metabolically important cell types, AgRP neurons of the hypothalamus and hepatocytes of the liver. We also provide examples dealing with the metabolic analysis of the Dq mutant mice after administration of CNO in vivo. The approaches described in this chapter can be applied to other members of the DREADD family and, of course, different cell types. It is likely that the use of DREADD technology will identify physiologically important signaling pathways that can be targeted for therapeutic purposes.

Key words

G-protein-coupled receptors Designer GPCRs G proteins Signal transduction Glucose homeostasis Food intake