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GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing.
J Clin Invest. 2005 Dec; 115(12):3634-40.JCI

Abstract

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 pharmacotherapeutical use of nicotinic acid is a strong flushing response. This side effect, although harmless, strongly affects patient compliance. In the present study, we show that mice lacking PUMA-G did not show nicotinic acid-induced flushing. In addition, flushing in response to nicotinic acid was also abrogated in the absence of cyclooxygenase type 1, and mice lacking prostaglandin D(2) (PGD(2)) and prostaglandin E(2) (PGE(2)) receptors had reduced flushing responses. The mouse orthologue of GPR109A, PUMA-G, is highly expressed in macrophages and other immune cells, and transplantation of wild-type bone marrow into irradiated PUMA-G-deficient mice restored the nicotinic acid-induced flushing response. Our data clearly indicate that GPR109A mediates nicotinic acid-induced flushing and that this effect involves release of PGE(2) and PGD(2), most likely from immune cells of the skin.

Authors+Show Affiliations

Institute of Pharmacology, University of Heidelberg, Heidelberg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16322797

Citation

Benyó, Zoltán, et al. "GPR109A (PUMA-G/HM74A) Mediates Nicotinic Acid-induced Flushing." The Journal of Clinical Investigation, vol. 115, no. 12, 2005, pp. 3634-40.
Benyó Z, Gille A, Kero J, et al. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest. 2005;115(12):3634-40.
Benyó, Z., Gille, A., Kero, J., Csiky, M., Suchánková, M. C., Nüsing, R. M., Moers, A., Pfeffer, K., & Offermanns, S. (2005). GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. The Journal of Clinical Investigation, 115(12), 3634-40.
Benyó Z, et al. GPR109A (PUMA-G/HM74A) Mediates Nicotinic Acid-induced Flushing. J Clin Invest. 2005;115(12):3634-40. PubMed PMID: 16322797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. AU - Benyó,Zoltán, AU - Gille,Andreas, AU - Kero,Jukka, AU - Csiky,Marion, AU - Suchánková,Marie Catherine, AU - Nüsing,Rolf M, AU - Moers,Alexandra, AU - Pfeffer,Klaus, AU - Offermanns,Stefan, PY - 2004/10/14/received PY - 2005/09/13/accepted PY - 2005/12/3/pubmed PY - 2006/2/7/medline PY - 2005/12/3/entrez SP - 3634 EP - 40 JF - The Journal of clinical investigation JO - J Clin Invest VL - 115 IS - 12 N2 - 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 pharmacotherapeutical use of nicotinic acid is a strong flushing response. This side effect, although harmless, strongly affects patient compliance. In the present study, we show that mice lacking PUMA-G did not show nicotinic acid-induced flushing. In addition, flushing in response to nicotinic acid was also abrogated in the absence of cyclooxygenase type 1, and mice lacking prostaglandin D(2) (PGD(2)) and prostaglandin E(2) (PGE(2)) receptors had reduced flushing responses. The mouse orthologue of GPR109A, PUMA-G, is highly expressed in macrophages and other immune cells, and transplantation of wild-type bone marrow into irradiated PUMA-G-deficient mice restored the nicotinic acid-induced flushing response. Our data clearly indicate that GPR109A mediates nicotinic acid-induced flushing and that this effect involves release of PGE(2) and PGD(2), most likely from immune cells of the skin. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/16322797/GPR109A__PUMA_G/HM74A__mediates_nicotinic_acid_induced_flushing_ DB - PRIME DP - Unbound Medicine ER -