MPI for Heart and Lung Research
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Project leaders: Dr. Sorin Tunaru, Dr. Sarah Tonack, Dr. Remy Bonnavion, Dr. Shun Lu ,Dr. Justin Mirus

PhD Students: Isabell Brandenburger

Technical Assistant: Kathrin Adolph

 

human non-olfactory GPCRs

Human non-olfactory G-protein-coupled receptors. Established drug targets are in red, orphan GPCRs are in green.

G-protein-coupled receptors (GPCRs) are the largest receptor family in mammals, and for more than 150 GPCRs no ligand has been described so far. One of the ongoing projects aims at the identification of new GPCR-ligand-pairs. We have identified a new receptor activated by lactate which plays an important role in the regulation of adipocyte lipolysis (Ahmed et al, 2010). Using an siRNA based approach to identify new ligand receptor pairs, we found that the EP3-prostanoid receptor is a receptor mediating the effects of ricinoleic acid, the major metabolite of castor oil (Tunaru et al, 2012). Besides research on new receptor ligand pairs, work on established important pharmacological receptors like the nicotinic acid receptor (HCA2/GPR109A) has been continued, and we have been able to elucidate the mechanisms underlying nicotinic acid induced flushing (Hanson et al, 2010), the mechanisms underlying the anti-atherogenic effect of nicotinic acid (Lukasova et al, 2011a) as well as the role of FFA2 and FFA3 in the regulation of insulin secretion (Tang et al, 2015). In addition, a role of the purinergic P2Y2 receptor in endothelial flow sensing and blood pressure regulation has recently been described by us (Wang et al., 2015). Work on these and related receptors has been summarized in several reviews (Blad et al, 2012; Lukasova et al, 2011b; Offermanns, 2014).

Literature

Wang S, Iring A, Strilic B, Albarrán Juárez J, Kaur H, Troidl K, Tonack S, Burbiel JC, Müller CE, Fleming I, Lundberg JO, Wettschureck N, Offermanns S (2015). P2Y2 and Gq/G11 control blood pressure by mediating endothelial mechanotransduction. J. Clin. Invest. 125: 3077-3086.

Tang C, Ahmed K, Gille A, Lu S, Gröne HJ, Tunaru S, Offermanns S (2015). Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat. Med. 21, 173-177

Offermanns S (2014). Free Fatty Acid (FFA) and Hydroxy Carboxylic Acid (HCA) Receptors. Annu. Rev. Pharmacol. Toxicol. 54, 407-434

Tunaru S, Althoff TF, Nusing RM, Diener M, Offermanns S (2012). Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP3 receptors. Proc. Natl. Acad. Sci. U. S. A. 109, 9179-9184

Blad CC, Tang C, Offermanns S (2012). G protein-coupled receptors for energy metabolites as new therapeutic targets. Nat. Rev. Drug. Discov. 11, 601-619

Lukasova M, Malaval C, Gille A, Kero J, Offermanns S (2011a). Nicotinic acid inhibits progression of atherosclerosis in mice through its receptor GPR109A expressed by immune cells. J. Clin. Invest. 121, 1163-1173

Lukasova M, Hanson J, Tunaru S, Offermanns S (2011b). Nicotinic acid (niacin): new lipid-independent mechanisms of action and therapeutic potential. Trends Pharmacol. Sci. 32, 700-707

Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, Ijzerman AP (2011). International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B). Pharmacol. Rev. 63, 269-290

Ahmed K, Tunaru S, Tang C, Müller M, Gille A, Sassmann A, Hanson J, and Offermanns S (2010). An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81. Cell Metab. 11, 311-19

Hanson J, Gille A, Zwykiel S, Lukasova M, Clausen BE, Ahmed K, Tunaru S, Wirth A, Offermanns S (2010). Keratinocytes express GPR109A and mediate epidermal effects of nicotinic acid and mono-Methyl fumarate via COX-2-dependent prostanoid formation J. Clin. Invest. 120, 2910-2919