GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing.

@article{Beny2005GPR109AM,
  title={GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing.},
  author={Zolt{\'a}n Beny{\'o} and Andreas Gille and Jukka Kero and Marion Csiky and Marie Catherine Such{\'a}nkov{\'a} and Rolf M. N{\"u}sing and Alexandra Moers and Klaus Pfeffer and Stefan Offermanns},
  journal={The Journal of clinical investigation},
  year={2005},
  volume={115 12},
  pages={
          3634-40
        }
}
Nicotinic acid (niacin) has long been used as an antidyslipidemic drug. Its special profile of actions, especially the rise in HDL-cholesterol levels induced by nicotinic acid, is unique among the currently available pharmacological tools to treat lipid disorders. Recently, a G-protein-coupled receptor, termed GPR109A (HM74A in humans, PUMA-G in mice), was described and shown to mediate the nicotinic acid-induced antilipolytic effects in adipocytes. One of the major problems of the… Expand
Role of HCA₂ (GPR109A) in nicotinic acid and fumaric acid ester-induced effects on the skin.
TLDR
Recent progress in the understanding of the mechanisms underlying HCA₂-mediated flushing is summarized, strategies to mitigate it are described and the potential link between flushing, HCA ₂ and the anti-psoriatic effects of FAE is discussed. Expand
Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid.
  • N. Pike
  • Chemistry, Medicine
  • The Journal of clinical investigation
  • 2005
TLDR
The involvement of GPR109A in the nicotinic acid-induced flushing response, a common side effect, raises interesting questions regarding the function of this receptor. Expand
The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target.
TLDR
Recent progress in understanding the physiological and pharmacological role of the nicotinic acid receptor is summarized and its potential use as a new target for the development of antidyslipidemic drugs to prevent and treat cardiovascular diseases is discussed. Expand
Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice.
TLDR
The early and late phases of the GPR109A-mediated cutaneous flushing reaction involve different epidermal cell types and prostanoid-forming enzymes, which will help to guide new efficient approaches to mitigate nicotinic acid-induced flushing and may help to exploit the potential antipsoriatic effects of G PR109A agonists in the skin. Expand
Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A.
TLDR
It is demonstrated that HM74A synergistically enhanced UTP- and bradykinin-mediated AA release in a pertussis toxin-sensitive manner in A431 cells, suggesting that alteration of AA signaling pathway can regulate gene expression via endogenous PPARs. Expand
beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice.
TLDR
The data suggest that the adverse side effect of cutaneous flushing is mediated by beta-arrestin1, but lowering of serum free fatty acid levels is not, and G protein-biased ligands that activate GPR109A in a beta-Arrestin-independent fashion may represent an improved therapeutic option for the treatment of dyslipidemia. Expand
Nicotinic Acid-Induced Flushing Is Mediated by Activation of Epidermal Langerhans Cells
The antidyslipidemic drug nicotinic acid (niacin) has been used for decades. One of the major problems of the therapeutical use of nicotinic acid is a strong cutaneous vasodilation called flushing,Expand
Nicotinic acid induces secretion of prostaglandin D2 in human macrophages: an in vitro model of the niacin flush.
TLDR
Evidence is provided that macrophages play a significant role in mediating the niacin flush and may lead to better strategies to eliminate this limiting side effect of nicotinic acid use. Expand
Nicotinic acid (niacin) receptor agonists: will they be useful therapeutic agents?
TLDR
New evidence indicates niacin directly inhibits diacylglycerol acyltransferase 2 (DGAT2) isolated from human hepatocytes, resulting in accelerated hepatic apolipoprotein (apo)B degradation and decreased apoB secretion, thus explaining reductions in VLDL and LDL in dyslipidemic patients. Expand
Langerhans cells release prostaglandin D2 in response to nicotinic acid.
TLDR
Results suggest that nicotinic acid mediates its flushing side effect by interacting with GPR109A on skin Langerhans cells, resulting in release of PGD(2). Expand
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PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect
TLDR
It is shown that the orphan G-protein-coupled receptor, 'protein upregulated in macrophages by interferon-γ' (mouse PUMA-G, human HM74), is highly expressed in adipose tissue and is a nicotinic acid receptor. Expand
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TLDR
It is shown that a novel GPCR, designated HM74b because of its high similarity to HM74, is a receptor for nicotinic acid, and this finding will open a new phase of research on the physiological role of nicotinics acid and will be a clue to develop novel antihyperlipidemic drugs. Expand
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Good possibilities for using nicotinic acid in the prevention and remission of atherosclerotic processes arise in connection with the activation of fibrinolysis and the reduction of the tendency toward platelet aggregation. Expand
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MCRTH2-dependent chemotaxis was inhibited by PTX and wortmannin, indicating dependence on Gi and PI 3-kinase signal transduction pathways and the first pharmacological and functional characterization of the mouse CRTH2 receptor is provided. Expand
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The finding that ingestion of niacin evokes the release of markedly increased quantities ofPGD2 in vivo in humans suggests that PGD2 is the mediator of niakin-induced vasodilation in humans. Expand
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It is demonstrated that acipimox is a satisfactory alternative to nicotinic acid in patients with hypertriglyceridaemia and no effects on laboratory parameters such as liver enzymes and uric acid were seen after treatment with acipIMox. Expand
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TLDR
In isolated slices from guinea-pig ears, nicotinic acid increased the level of cyclic AMP; this effect was inhibited by indomethacin; the stimulating action of prostaglandin E1 on the cyclicAMP level of the ear slices was not inhibited byIndomethACin. Expand
Molecular Identification of High and Low Affinity Receptors for Nicotinic Acid*
TLDR
The identification of the G protein-coupled receptor HM74 as a low affinity receptor for nicotinic acid and the subsequent identification of HM74A in follow-up bioinformatics searches and demonstrate that it acts as a high affinity receptors for Nicotinic Acid and other compounds with related pharmacology. Expand
The nicotinic acid receptor–a new mechanism for an old drug
TLDR
Research on signalling through the nicotinic acid receptor might give rise to novel and more effective methods to interfere with fatty-acid metabolism, with insulin resistance, hyperlipidaemia, and atherosclerosis as target diseases. Expand
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