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.
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Acknowledgements
This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH. We thank Ms. Yinghong Cui and Mr. Matthew Stern for excellent technical support. We are also very grateful to the following three individuals who generously shared their expertise and many valuable reagents with us: Dr. Bryan L. Roth (The University of North Carolina, Chapel Hill, NC), Dr. Michael Krashes (NIDDK, NIH, Bethesda, MD), and Dr. Morris J. Birnbaum (The University of Pennsylvania, Philadelphia, PA).
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Rossi, M., Cui, Z., Nakajima, Ki., Hu, J., Zhu, L., Wess, J. (2015). Virus-Mediated Expression of DREADDs for In Vivo Metabolic Studies. In: Filizola, M. (eds) G Protein-Coupled Receptors in Drug Discovery. Methods in Molecular Biology, vol 1335. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2914-6_14
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DOI: https://doi.org/10.1007/978-1-4939-2914-6_14
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