Meet Dr. GPCR Summit Partners
Designer G protein-coupled receptors as tools to identify novel targets for antidiabetic and anti-obesity drugs
Tuesday, 09/14/2021 @ 9:00 AM - EST
- Dr. Jürgen Wess -
- NIH-NIDDK -
- Bethesda, MD, USA -
Abstract
About 1/3 of FDA-approved drugs target one or more G protein-coupled receptors (GPCRs), indicative of the preeminent therapeutic importance of this class of receptors. Most metabolic processes are regulated by the activity of multiple GPCRs. A specific GPCR interacts with one or more of the four major classes of heterotrimeric G proteins (Gs, Gi, Gq, and G12).
Characteristically, a particular GPCR is expressed in multiple tissues and cell types. In addition, highly selective ligands (agonists or antagonists) are not available for many GPCRs. As a result, it has proven very difficult to identify them in vivo metabolic roles of a particular GPCR expressed by a specific cell type. The availability of designer GPCRs known as DREADDs (Designer Receptors Exclusively Activated by a Designer Drug) has greatly advanced our knowledge about the metabolic roles of activating specific classes of G proteins in distinct cell types. The most commonly used DREADDs are mutant muscarinic acetylcholine receptors that can couple to either Gs, Gi, Gq, or G12.
These DREADDs can be selectively activated by clozapine-N-oxide (CNO), a synthetic drug, but are virtually unresponsive when exposed to acetylcholine, the endogenous muscarinic receptor agonist. CNO is pharmacologically inert when used in the proper concentration/dose range. During the past decade, my lab has generated and analyzed mutant mice that express specific DREADDs in distinct cell types that are critically involved in regulating glucose and energy homeostasis. Systemic analysis of these various DREADD strains has shed novel light on the metabolic roles of specific GPCR signaling pathways.
My talk will focus primarily on the analysis of mutant mouse strains expressing DREADDs in specific peripheral cell types, including alpha- and beta-cells of the endocrine pancreas and adipocytes. The new data emerging from these studies should guide the development of novel classes of antidiabetic and anti-obesity drugs.
Author list and Affiliations
- Jürgen Wess Molecular Signaling Section, Lab. of Bioorganic Chemistry, NIH-NIDDK, Bethesda, MD 20892-0810, USA
About Dr. Jürgen Wess
Jürgen Wess, Ph.D., is the Chief of the Molecular Signaling Section, Laboratory of Bioorganic Chemistry, NIDDK, NIH, Bethesda, MD, USA. He received his Ph.D. in Pharmacology from the Goethe University in Frankfurt (Germany) and obtained postdoctoral training at the NIH in Bethesda, MD. Dr. Wess is a pharmacologist with a primary interest in the general area of G protein-coupled receptors (GPCRs). Currently, the major goal of his research is to identify GPCRs or GPCR-linked signaling pathways that can be targeted for the treatment of diabetes and obesity.
Dr. Jürgen Wess on the web
Meet Dr. GPCR Summit Partners
