GPR109A and vascular inflammation - PubMed (original) (raw)

Review

GPR109A and vascular inflammation

Joshua T Chai et al. Curr Atheroscler Rep. 2013 May.

Abstract

GPR109A has generated expanding interest since its discovery as the receptor for niacin a decade ago, along with deorphanisation as the receptor for endogenous ligand 3-hydroxy-butyrate shortly after. This interest is generated especially because of the continuing exploration of niacin's "pleiotropic" mechanisms of action and its potential in the "cross-talk" between metabolic and inflammatory pathways. As GPR109A's primary pharmacological ligand in clinical use, niacin has been used for over 50 years in the treatment of cardiovascular disease, mainly due to its favourable effects on plasma lipoproteins. However, it has become apparent that niacin also possesses lipoprotein-independent effects that influence inflammatory pathways mediated through GPR109A. In addition to its G-protein-mediated effects, recent evidence has emerged to support alternative GPR109A signalling via adaptive protein β-arrestins. In this article, we consider the role of GPR109A and its downstream effects in the context of atherosclerosis and vascular inflammation, along with insights into strategy for future drug development.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

Diagram showing the putative GPR109A downstream signalling mechanisms. α, β, γ: G-protein subunits; β-Arr: β-arrestin; numbers refer to respective references. GPR109A activation results in G-protein–coupled receptor kinase (GRK)-mediated self-phosphorylation and recruitment of β-arrestins. In addition to mediating GPR109A receptor internalisation and recycling, β-arrestins also directly mediate downstream signalling independent of the G-protein pathways

Similar articles

Cited by

References

    1. Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, Ijzerman AP. International union of basic and clinical pharmacology. Lxxxii: nomenclature and classification of hydroxy-carboxylic acid receptors (gpr81, gpr109a, and gpr109b) Pharmacol Rev. 2011;63:269–290. doi: 10.1124/pr.110.003301. - DOI - PubMed
    1. Altschul R, Hoffer A, Stephen JD. Influence of nicotinic acid on serum cholesterol in man. Arch Biochem Biophys. 1955;54:558–559. doi: 10.1016/0003-9861(55)90070-9. - DOI - PubMed
    1. Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, et al. Molecular identification of nicotinic acid receptor. Biochem Biophys Res Commun. 2003;303:364–369. doi: 10.1016/S0006-291X(03)00342-5. - DOI - PubMed
    1. Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, et al. Puma-g and hm74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med. 2003;9:352–355. doi: 10.1038/nm824. - DOI - PubMed
    1. Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, et al. Molecular identification of high and low affinity receptors for nicotinic acid. J Biol Chem. 2003;278:9869–9874. doi: 10.1074/jbc.M210695200. - DOI - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources