International union of basic and clinical pharmacology. LXXXII: Nomenclature and classification of hydroxy-carboxylic acid receptors (GPR81, GPR109A, and GPR109B)

Pharmacological Reviews

Volumn 63, Issue 2, 2011, Pages 269-290

  Offermanns, Stefan ^a,b   Colletti, Steven L ^c   Lovenberg, Timothy W ^d   Semple, Graeme ^e   Wise, Alan ^g,h   Ijzerman, Adriaan P ^f  

^a MAX PLANCK INSTITUTE FOR HEART AND LUNG RESEARCH   (Germany)

^b GOETHE UNIVERSITY   (Germany)

^c MERCK RESEARCH LABORATORIES   (United States)

^d JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

^e ARENA PHARMACEUTICALS   (United States)

^f LEIDEN UNIVERSITY   (Netherlands)

^g TPP Global Development   (United Kingdom)

^h Scottish Institute for Enterprise   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; 3 PYRIDINE ACETIC ACID; 5 METHIONINE NICOTINIC ACID; 6 METHIONINE NICOTINIC ACID; ACETIC ACID DERIVATIVE; ACIFRAN; ACIPIMOX; ANTHRANILIC ACID DERIVATIVE; CARBOXYLIC ACID DERIVATIVE; COMPLEMENTARY DNA; FORSKOLIN; FURAN DERIVATIVE; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR GPR109A; G PROTEIN COUPLED RECEPTOR GPR109B; G PROTEIN COUPLED RECEPTOR GPR81; HYDROXYCARBOXYLIC ACID; HYDROXYCARBOXYLIC ACID RECEPTOR; LACTIC ACID; MK 0354; MK 6892; NICOTINAMIDE; NICOTINIC ACID; NICOTINIC ACID DERIVATIVE; NICOTINIC RECEPTOR; OXINIACIC ACID; PROPIONIC ACID; PYRAZINE DERIVATIVE; PYRAZOLE 3 CARBOXYLIC ACID; PYRAZOLE DERIVATIVE; PYRIDAZINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADIPOCYTE; ALLOSTERISM; ARTICLE; BINDING AFFINITY; CARBOXYLATION; CLINICAL PHARMACOLOGY; CLINICAL TRIAL (TOPIC); DRUG BINDING; DRUG FORMULATION; DRUG INHIBITION; DRUG NOMENCLATURE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG RELEASE; GENE CONTROL; GENE EXPRESSION; GENE STRUCTURE; HUMAN; IC 50; IN VITRO STUDY; IN VIVO STUDY; LACTATE BLOOD LEVEL; LIPOLYSIS; MOLECULAR MODEL; NONHUMAN; PATENT; PHYLOGENETIC TREE; PRIORITY JOURNAL; PROTEIN CONFORMATION; RECEPTOR DOWN REGULATION; RODENT; SEQUENCE ALIGNMENT; SIGNAL TRANSDUCTION; SITE DIRECTED MUTAGENESIS; STRUCTURE ACTIVITY RELATION; VASODILATATION;

ANIMALS; CLONING, MOLECULAR; HUMANS; INTERNATIONAL AGENCIES; MODELS, MOLECULAR; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, NICOTINIC; TERMINOLOGY AS TOPIC;

EID: 79955769365     PISSN: 00316997     EISSN: 15210081     Source Type: Journal    
DOI: 10.1124/pr.110.003301     Document Type: Article

References (128)

1. Ahmed K, Tunaru S, Langhans CD, Hanson J, Michalski CW, Kölker S, Jones PM, Okun JG, and Offermanns S (2009a) Deorphanization of GPR109B as a receptor for the beta-oxidation intermediate 3-OH-octanoic acid and its role in the regulation of lipolysis. J Biol Chem 284:21928-21933.
2. Ahmed K, Tunaru S, and Offermanns S (2009b) GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors. Trends Pharmacol Sci 30:557-562.
3. 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 11:311-319.
4. Aktories K, Jakobs KH, and Schultz G (1980a) Nicotinic acid inhibits adipocyte adenylate cyclase in a hormone-like manner. FEBS Lett 115:11-14.
5. Aktories K, Schultz G, and Jakobs KH (1980b) Regulation of adenylate cyclase activity in hamster adipocytes. Inhibition by prostaglandins, alpha-adrenergic agonists and nicotinic acid. Naunyn Schmiedebergs Arch Pharmacol 312:167-173.
6. Aktories K, Schultz G, and Jakobs KH (1983) Islet-activating protein prevents nicotinic acid-induced GTPase stimulation and GTP but not GTP gamma S-induced adenylate cyclase inhibition in rat adipocytes. FEBS Lett 156:88-92.
7. Altschul R, Hoffer A, and Stephen JD (1955) Influence of nicotinic acid on serum cholesterol in man. Arch Biochem 54:558-559.
8. Benyó Z, Gille A, Bennett CL, Clausen BE, and Offermanns S (2006) Nicotinic acid-induced flushing is mediated by activation of epidermal langerhans cells. Mol Pharmacol 70:1844-1849.
9. Benyo ́ Z, Gille A, Kero J, Csiky M, Suchánkova ́ MC, Nü sing RM, Moers A, Pfeffer K, and Offermanns S (2005) GPR109A (PUMA-G/HM74A) mediates nicotinic acidinduced flushing. J Clin Invest 115:3634-3640.
10. Bjarnado ́ttir TK, Gloriam DE, Hellstrand SH, Kristiansson H, Fredriksson R, and Schiöth HB (2006) Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Genomics 88:263-273.
11. Boatman PD, Richman JG, and Semple G (2008) Nicotinic acid receptor agonists. J Med Chem 51:7653-7662.
12. Bodor ET and Offermanns S (2008) Nicotinic acid: an old drug with a promising future. Br J Pharmacol 153 (Suppl 1):S68-S75.
13. Boyd AE 3rd, Giamber SR, Mager M, and Lebovitz HE (1974) Lactate inhibition of lipolysis in exercising man. Metabolism 23:531-542.
14. Brink C, Dahle ́n SE, Drazen J, Evans JF, Hay DW, Rovati GE, Serhan CN, Shimizu T, and Yokomizo T (2004) International Union of Pharmacology XLIV. Nomenclature for the oxoeicosanoid receptor. Pharmacol Rev 56:149-157.
15. Brooks GA and Mercier J (1994) Balance of carbohydrate and lipid utilization during exercise: the "crossover" concept. J Appl Physiol 76:2253-2261.
16. Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P, et al. (2001) Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 345:1583-1592.
17. Butcher RW, Baird CE, and Sutherland EW (1968) Effects of lipolytic and antilipolytic substances on adenosine 3_,5_-monophosphate levels in isolated fat cells. J Biol Chem 243:1705-1712.
18. Cai TQ, Ren N, Jin L, Cheng K, Kash S, Chen R, Wright SD, Taggart AK, and Waters MG (2008) Role of GPR81 in lactate-mediated reduction of adipose lipolysis. Biochem Biophys Res Commun 377:987-991.
19. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, and Friedewald W (1986) Fifteen year mortality in Coronary Drug Project patients: longterm benefit with niacin. J Am Coll Cardiol 8:1245-1255.
20. Capuzzi DM, Guyton JR, Morgan JM, Goldberg AC, Kreisberg RA, Brusco OA, and Brody J (1998) Efficacy and safety of an extended-release niacin (Niaspan): a long-term study. Am J Cardiol 82:74U-81U; discussion 85U-86U.
21. Carlson LA (1963) Studies on the effect of nicotinic acid on catecholamine stimulated lipolysis in adipose tissue in vitro. Acta Med Scand 173:719-722.
22. Carlson LA (2005) Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review. J Intern Med 58:94-114.
23. Carlson LA and Oro L (1962) The effect of nicotinic acid on the plasma free fatty acid; demonstration of a metabolic type of sympathicolysis. Acta Med Scand 172:641-645.
24. Cayen MN, Kallai-Sanfacon MA, Dubuc J, Greselin E, and Dvornik D (1982) Evaluation of the lipid-lowering activity of AY-25,712 in rats. Atherosclerosis 45:267-279.
25. Cheng K, Wu TJ, Wu KK, Sturino C, Metters K, Gottesdiener K, Wright SD, Wang Z, O'Neill G, Lai E, et al. (2006) Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans. Proc Natl Acad Sci USA 103:6682-6687.
26. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, et al. (2007) High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318:1258-1265.
27. Coronary Drug Project Research Group (1975) Clofibrate and niacin in coronary heart disease. Jama 231:360-381.
28. Costa CG, Dorland L, Holwerda U, de Almeida IT, Poll-The BT, Jakobs C, and Duran M (1998) Simultaneous analysis of plasma free fatty acids and their 3-hydroxy analogs in fatty acid beta-oxidation disorders. Clin Chem 44:463-471.
29. Cresci GA, Thangaraju M, Mellinger JD, Liu K, and Ganapathy V (2010) Colonic gene expression in conventional and germ-free mice with a focus on the butyrate receptor GPR109A and the butyrate transporter SLC5A8. J Gastrointest Surg 14:449-461.
30. Deng Q, Frie JL, Marley DM, Beresis RT, Ren N, Cai TQ, Taggart AK, Cheng K, Carballo-Jane E, Wang J, et al. (2008) Molecular modeling aided design of nicotinic acid receptor GPR109A agonists. Bioorg Med Chem Lett 18:4963-4967.
31. Digby JE, Lee JM, and Choudhury RP (2009) Nicotinic acid and the prevention of coronary artery disease. Curr Opin Lipidol 20:321-326.
32. DiGirolamo M, Newby FD, and Lovejoy J (1992) Lactate production in adipose tissue: a regulated function with extra-adipose implications. Faseb J 6:2405-2412.
33. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, and Sul HS (2007) Regulation of lipolysis in adipocytes. Annu Rev Nutr 27:79-101.
34. Exton JH (1996) Regulation of phosphoinositide phospholipases by hormones, neurotransmitters, and other agonists linked to G proteins. Annu Rev Pharmacol Toxicol 36:481-509.
35. Fredholm BB (1971) The effect of lactate in canine subcutaneous adipose tissue in situ. Acta Physiol Scand 81:110-123.
36. Ge H, Weiszmann J, Reagan JD, Gupte J, Baribault H, Gyuris T, Chen JL, Tian H, and Li Y (2008) Elucidation of signaling and functional activities of an orphan GPCR, GPR81. J Lipid Res 49:797-803.
37. Gharbaoui T, Skinner PJ, Shin YJ, Averbuj C, Jung JK, Johnson BR, Duong T, Decaire M, Uy J, Cherrier MC, et al. (2007) Agonist lead identification for the high affinity niacin receptor GPR109a. Bioorg Med Chem Lett 17:4914-4919.
38. Gille A, Bodor ET, Ahmed K, and Offermanns S (2008) Nicotinic acid: pharmacological effects and mechanisms of action. Annu Rev Pharmacol Toxicol 48:79-106.
39. Guyton JR (2007) Niacin in cardiovascular prevention: mechanisms, efficacy, and safety. Current Opinion in Lipidology 18:415-420.
40. Hagström-Toft E, Enoksson S, Moberg E, Bolinder J, and Arner P (1997) Absolute concentrations of glycerol and lactate in human skeletal muscle, adipose tissue, and blood. Am J Physiol 273:E584-E592.
41. Hanson J, Gille A, Zwykiel S, Lukasova M, Clausen BE, Ahmed K, Tunaru S, Wirth A, and Offermanns S (2010) Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice. J Clin Invest 120:2910-2919.
42. Hernandez M, Wright SD, and Cai TQ (2007) Critical role of cholesterol ester transfer protein in nicotinic acid-mediated HDL elevation in mice. Biochem Biophys Res Commun 355:1075-1080.
43. Hoefnagel JJ, Thio HB, Willemze R, and Bouwes Bavinck JN (2003) Long-term safety aspects of systemic therapy with fumaric acid esters in severe psoriasis. Br J Dermatol 149:363-369.
44. Hofer AM and Brown EM (2003) Extracellular calcium sensing and signalling. Nat Rev Mol Cell Biol 4:530-538.
45. Hosoi T, Koguchi Y, Sugikawa E, Chikada A, Ogawa K, Tsuda N, Suto N, Tsunoda S, Taniguchi T, and Ohnuki T (2002) Identification of a novel human eicosanoid receptor coupled to G(i/o). J Biol Chem 277:31459-31465.
46. Huckabee WE (1958) Relationships of pyruvate and lactate during anaerobic metabolism. I. Effects of infusion of pyruvate or glucose and of hyperventilation. J Clin Invest 37:244-254.
47. IJzerman AP, Offermanns S, Waters MG, and Wise A (2010) Nicotinic acid receptor family. IUPHAR database (IUPHAR-DB). Available at: http://www.iuphar-db.org/DATABASE/FamilyMenuForward?familyId_48.
48. Imbriglio JE, Chang S, Liang R, Raghavan S, Schmidt D, Smenton A, Tria S, Schrader TO, Jung JK, Esser C, et al. (2009) GPR109a agonists. Part 1: 5-Alkyl and 5-aryl-pyrazole-tetrazoles as agonists of the human orphan G-protein coupled receptor GPR109a. Bioorg Med Chem Lett 19:2121-2124.
49. Irukayama-Tomobe Y, Tanaka H, Yokomizo T, Hashidate-Yoshida T, Yanagisawa M, and Sakurai T (2009) Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B. Proc Natl Acad Sci USA 106:3930-3934.
50. Issekutz B Jr and Miller HI (1962) Plasma free fatty acids during exercise and the effect of lactic acid. Proc Soc Exp Biol Med 110:237-239.
51. Jaakola VP, Griffith MT, Hanson MA, Cherezov V, Chien EY, Lane JR, Ijzerman AP, and Stevens RC (2008) The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 322:1211-1217.
52. Jansson PA, Larsson A, Smith U, and Lönnroth P (1994) Lactate release from the subcutaneous tissue in lean and obese men. J Clin Invest 93:240-246.
53. Jeninga EH, Bugge A, Nielsen R, Kersten S, Hamers N, Dani C, Wabitsch M, Berger R, Stunnenberg HG, Mandrup S, et al. (2009) Peroxisome proliferator-activated receptor gamma regulates expression of the anti-lipolytic G-protein-coupled receptor 81 (GPR81/Gpr81). J Biol Chem 284:26385-26393.
54. Jones CE, Holden S, Tenaillon L, Bhatia U, Seuwen K, Tranter P, Turner J, Kettle R, Bouhelal R, Charlton S, et al. (2003) Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils. Mol Pharmacol 63:471-477.
55. Jones PM, Tjoa S, Fennessey PV, Goodman SI, and Bennett MJ (2002) Addition of quantitative 3-hydroxy-octadecanoic acid to the stable isotope gas chromatography-mass spectrometry method for measuring 3-hydroxy fatty acids. Clin Chem 48:176-179.
56. Joy T and Hegele RA (2008) Is raising HDL a futile strategy for atheroprotection? Nat Rev Drug Discov 7:143-155.
57. Jung JK, Johnson BR, Duong T, Decaire M, Uy J, Gharbaoui T, Boatman PD, Sage CR, Chen R, Richman JG, et al. (2007) Analogues of acifran: agonists of the high and low affinity niacin receptors, GPR109a and GPR109b. J Med Chem 50:1445-1448.
58. Kamanna VS, Ganji SH, and Kashyap ML (2009) The mechanism and mitigation of niacin-induced flushing. Int J Clin Pract 63:1369-1377.
59. Kamanna VS and Kashyap ML (2008) Mechanism of action of niacin. Am J Cardiol 101:20B-26B.
60. Kappos L, Gold R, Miller DH, Macmanus DG, Havrdova E, Limmroth V, Polman CH, Schmierer K, Yousry TA, Yang M, et al. (2008) Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 372:1463-1472.
61. Knowles HJ, te Poele RH, Te Poole R, Workman P, and Harris AL (2006) Niacin induces PPARgamma expression and transcriptional activation in macrophages via HM74 and HM74a-mediated induction of prostaglandin synthesis pathways. Biochem Pharmacol 71:646-656.
62. Kontush A and Chapman MJ (2006) Antiatherogenic small, dense HDL-guardian angel of the arterial wall? Nat Clin Pract Cardiovasc Med 3:144-153.
63. Kostylina G, Simon D, Fey MF, Yousefi S, and Simon HU (2008) Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A). Cell Death Differ 15:134-142.
64. Kreisberg RA (1980) Lactate homeostasis and lactic acidosis. Ann Intern Med 92: 227-237.
65. Lai E, Waters MG, Tata JR, Radziszewski W, Perevozskaya I, Zheng W, Wenning L, Connolly DT, Semple G, Johnson-Levonas AO, et al. (2008) Effects of a niacin receptor partial agonist, MK-0354, on plasma free fatty acids, lipids, and cutaneous flushing in humans. J Clin Lipidol 2:375-383.
66. Lee DK, Nguyen T, Lynch KR, Cheng R, Vanti WB, Arkhitko O, Lewis T, Evans JF, George SR, and O'Dowd BF (2001) Discovery and mapping of ten novel G proteincoupled receptor genes. Gene 275:83-91.
67. Li G, Shi Y, Huang H, Zhang Y, Wu K, Luo J, Sun Y, Lu J, Benovic JL, and Zhou N (2010) Internalization of the human nicotinic acid receptor GPR109A is regulated by Gi, GRK2, and arrestin3. J Biol Chem 285:22605-22618.
68. Liu C, Wu J, Zhu J, Kuei C, Yu J, Shelton J, Sutton SW, Li X, Yun SJ, Mirzadegan T, et al. (2009) Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81. J Biol Chem 284:2811-2822.
69. Lorenzen A, Stannek C, Lang H, Andrianov V, Kalvinsh I, and Schwabe U (2001) Characterization of a G protein-coupled receptor for nicotinic acid. Mol Pharmacol 59:349-357.
70. Maciejewski-Lenoir D, Richman JG, Hakak Y, Gaidarov I, Behan DP, and Connolly DT (2006) Langerhans cells release prostaglandin D2 in response to nicotinic acid. J Invest Dermatol 126:2637-2646.
71. Mahboubi K, Witman-Jones T, Adamus JE, Letsinger JT, Whitehouse D, Moorman AR, Sawicki D, Bergenhem N, and Ross SA (2006) Triglyceride modulation by acifran analogs: activity towards the niacin high and low affinity G proteincoupled receptors HM74A and HM74. Biochem Biophys Res Commun 340:482-490.
72. Marbach EP and Weil MH (1967) Rapid enzymatic measurement of blood lactate and pyruvate. Use and significance of metaphosphoric acid as a common precipitant. Clin Chem 13:314-325.
73. Martin PM, Ananth S, Cresci G, Roon P, Smith S, and Ganapathy V (2009) Expression and localization of GPR109A (PUMA-G/HM74A) mRNA and protein in mammalian retinal pigment epithelium. Mol Vis 15:362-372.
74. Martres P (2009) HM74a agonists: will they be the new generation of nicotinic acid? Curr Top Med Chem 9:428-435.
75. McKenney J, Bays H, Koren M, Ballantyne CM, Paolini JF, Mitchel Y, Betteridge A, Kuznetsova O, Sapre A, Sisk CM, et al. (2010) Safety of extended-release niacin/ laropiprant in patients with dyslipidemia. J Clin Lipidol 4:105-112.e1.
76. Meyers CD, Kamanna VS, and Kashyap ML (2004) Niacin therapy in atherosclerosis. Curr Opin Lipidol 15:659-665.
77. Morrow JD, Parsons WG 3rd, and Roberts LJ 2nd (1989) Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid. Prostaglandins 38:263-274.
78. Niessner H and Beutler E (1973) Fluorometric analysts of glycolytic intermediates in human red blood cells. Biochem Med 8:123-134.
79. Nomura H, Nielsen BW, and Matsushima K (1993) Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors. Int Immunol 5:1239-1249.
80. Nugteren-Huying WM, van der Schroeff JG, Hermans J, and Suurmond D (1990) Fumaric acid therapy for psoriasis: a randomized, double-blind, placebo-controlled study. J Am Acad Dermatol 22:311-312.
81. Oberwittler H and Baccara-Dinet M (2006) Clinical evidence for use of acetyl salicylic acid in control of flushing related to nicotinic acid treatment. Int J Clin Pract 60:707-715.
82. Offermanns S (2006) The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target. Trends Pharmacol Sci 27:384-390.
83. Osnes JB and Hermansen L (1972) Acid-base balance after maximal exercise of short duration. J Appl Physiol 32:59-63.
84. Owen OE, Felig P, Morgan AP, Wahren J, and Cahill GF Jr (1969) Liver and kidney metabolism during prolonged starvation. J Clin Invest 48:574-583.
85. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, et al. (2000) Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289:739-745.
86. Paolini JF, Mitchel YB, Reyes R, Kher U, Lai E, Watson DJ, Norquist JM, Meehan AG, Bays HE, Davidson M, et al. (2008) Effects of laropiprant on nicotinic acidinduced flushing in patients with dyslipidemia. Am J Cardiol 101:625-630.
87. Qvisth V, Hagström-Toft E, Moberg E, Sjöberg S, and Bolinder J (2007) Lactate release from adipose tissue and skeletal muscle in vivo: defective insulin regulation in insulin-resistant obese women. Am J Physiol Endocrinol Metab 292:E709-E714.
88. Raghavan S, Tria GS, Shen HC, Ding FX, Taggart AK, Ren N, Wilsie LC, Krsmanovic ML, Holt TG, Wolff MS, et al. (2008) Tetrahydro anthranilic acid as a surrogate for anthranilic acid: Application to the discovery of potent niacin receptor agonists. Bioorg Med Chem Lett 18:3163-3167.
89. Reich K, Thaci D, Mrowietz U, Kamps A, Neureither M, and Luger T (2009) Efficacy and safety of fumaric acid esters in the long-term treatment of psoriasis-a retrospective study (FUTURE). J Dtsch Dermatol Ges 7:603-611.
90. Ren N, Kaplan R, Hernandez M, Cheng K, Jin L, Taggart AK, Zhu AY, Gan X, Wright SD, and Cai TQ (2009) Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G). J Lipid Res 50:908-914.
91. Richman JG, Kanemitsu-Parks M, Gaidarov I, Cameron JS, Griffin P, Zheng H, Guerra NC, Cham L, Maciejewski-Lenoir D, Behan DP, et al. (2007) Nicotinic acid receptor agonists differentially activate downstream effectors. J Biol Chem 282: 18028-18036.
92. Schaub A, Fütterer A, and Pfeffer K (2001) PUMA-G, an IFN-gamma-inducible gene in macrophages is a novel member of the seven transmembrane spanning receptor superfamily. Eur J Immunol 31:3714-3725.
93. Schmidt D, Smenton A, Raghavan S, Carballo-Jane E, Lubell S, Ciecko T, Holt TG, Wolff M, Taggart A, Wilsie L, et al. (2009) Pyrazole acids as niacin receptor agonists for the treatment of dyslipidemia. Bioorg Med Chem Lett 19:4768-4772.
94. Schweckendiek W (1959) [Treatment of psoriasis vulgaris.]. Med Monatsschr 13: 103-104.
95. Seki K, Isegawa J, Fukuda M, and Ohki M (1984) Studies on hypolipidemic agents. II. Synthesis and pharmacological properties of alkylpyrazole derivatives. Chem Pharm Bull 32:1568-1577.
96. Semple G, Skinner PJ, Gharbaoui T, Shin YJ, Jung JK, Cherrier MC, Webb PJ, Tamura SY, Boatman PD, Sage CR, et al. (2008) 3-(1H-tetrazol-5-yl)-1,4,5,6- tetrahydro-cyclopentapyrazole (MK-0354): a partial agonist of the nicotinic acid receptor, G-protein coupled receptor 109a, with antilipolytic but no vasodilatory activity in mice. J Med Chem 51:5101-5108.
97. Senior B and Loridan L (1968) Direct regulatory effect of ketones on lipolysis and on glucose concentrations in man. Nature 219:83-84.
98. Shen HC (2009) Acyl hydroxypyrazoles as novel agonists for high-affinity nicotinic acid receptor GPR109A: WO2008051403. Expert Opin Ther Pat 19:1149-1155.
99. Shen HC and Colletti SL (2009) Novel patent publications on high-affinity nicotinic acid receptor agonists. Expert Opin Ther Pat 19:957-967.
100. Shen HC, Ding FX, Deng Q, Wilsie LC, Krsmanovic ML, Taggart AK, Carballo-Jane E, Ren N, Cai TQ, Wu TJ, et al. (2009) Discovery of novel tricyclic full agonists for the G-protein-coupled niacin receptor 109A with minimized flushing in rats. J Med Chem 52:2587-2602.
101. Shen HC, Ding FX, Luell S, Forrest MJ, Carballo-Jane E, Wu KK, Wu TJ, Cheng K, Wilsie LC, Krsmanovic ML, et al. (2007a) Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor. J Med Chem 50:6303-6306.
102. Shen HC, Ding FX, Raghavan S, Deng Q, Luell S, Forrest MJ, Carballo-Jane E, Wilsie LC, Krsmanovic ML, Taggart AK, et al. (2010) Discovery of a biaryl cyclohexene carboxylic acid (MK-6892): a potent and selective high affinity niacin receptor full agonist with reduced flushing profiles in animals as a preclinical candidate. J Med Chem 53:2666-2670.
103. Shen HC, Szymonifka MJ, Kharbanda D, Deng Q, Carballo-Jane E, Wu KK, Wu TJ, Cheng K, Ren N, Cai TQ, et al. (2007b) Discovery of orally bioavailable and novel urea agonists of the high affinity niacin receptor GPR109A. Bioorg Med Chem Lett 17:6723-6728.
104. Shen HC, Taggart AKP, Wilsie LC, Waters MG, Hammond ML, Tata JR, and Colletti SL (2008) Discovery of pyrazolopyrimidines as the first class of allosteric agonists for the high affinity nicotinic acid receptor GPR109A. Bioorg Med Chem Lett 18:4948-4951.
105. Skinner PJ, Cherrier MC, Webb PJ, Sage CR, Dang HT, Pride CC, Chen R, Tamura SY, Richman JG, Connolly DT, et al. (2007a) 3-Nitro-4-amino benzoic acids and 6-amino nicotinic acids are highly selective agonists of GPR109b. Bioorg Med Chem Lett 17:6619-6622.
106. Skinner PJ, Cherrier MC, Webb PJ, Shin YJ, Gharbaoui T, Lindstrom A, Hong V, Tamura SY, Dang HT, Pride CC, et al. (2007b) Fluorinated pyrazole acids are agonists of the high affinity niacin receptor GPR109a. Bioorg Med Chem Lett 17:5620-5623.
107. Skinner PJ, Webb PJ, Sage CR, Dang TH, Pride CC, Chen R, Tamura SY, Richman JG, Connolly DT, and Semple G (2009) 5-N,N-Disubstituted 5-aminopyrazole-3- carboxylic acids are highly potent agonists of GPR109b. Bioorg Med Chem Lett 19:4207-4209.
108. Soga T, Kamohara M, Takasaki J, Matsumoto S, Saito T, Ohishi T, Hiyama H, Matsuo A, Matsushime H, and Furuichi K (2003) Molecular identification of nicotinic acid receptor. Biochem Biophys Res Commun 303:364-369.
109. Stern RH, Spence JD, Freeman DJ, and Parbtani A (1991) Tolerance to nicotinic acid flushing. Clin Pharmacol Ther 50:66-70.
110. Taggart AK, Kero J, Gan X, Cai TQ, Cheng K, Ippolito M, Ren N, Kaplan R, Wu K, Wu TJ, et al. (2005) (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem 280:26649-26652.
111. Tang H, Lu JY, Zheng X, Yang Y, and Reagan JD (2008) The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. Biochem Biophys Res Commun 375:562-565.
112. Tang Y, Zhou L, Gunnet JW, Wines PG, Cryan EV, and Demarest KT (2006) Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A. Biochem Biophys Res Commun 345:29-37.
113. Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, and Grace KA (2004) Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation 110:3512-3517.
114. Taylor AJ, Villines TC, Stanek EJ, Devine PJ, Griffen L, Miller M, Weissman NJ, and Turco M (2009) Extended-release niacin or ezetimibe and carotid intimamedia thickness. N Engl J Med 361:2113-2122.
115. Thangaraju M, Cresci GA, Liu K, Ananth S, Gnanaprakasam JP, Browning DD, Mellinger JD, Smith SB, Digby GJ, Lambert NA, et al. (2009) GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res 69:2826-2832.
116. Trudeau F, Bernier S, de Glisezinski I, Crampes F, Dulac F, and Riviere D (1999) Lack of antilipolytic effect of lactate in subcutaneous abdominal adipose tissue during exercise. J Appl Physiol 86:1800-1804.
117. Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, and Offermanns S (2003) PUMA-G and HM74 are receptors for nicotinic acid and mediate its antilipolytic effect. Nat Med 9:352-355.
118. Tunaru S, Lättig J, Kero J, Krause G, and Offermanns S (2005) Characterization of determinants of ligand binding to the nicotinic acid receptor GPR109A (HM74A/ PUMA-G). Mol Pharmacol 68:1271-1280.
119. Turrell ES and Robinson S (1942) The acid-base equilibrium of the blood in exercise. Am J Physiol 137:742-745.
120. van der Hoorn JW, de Haan W, Berbe ́e JF, Havekes LM, Jukema JW, Rensen PC, and Princen HM (2008) Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice. Arterioscler Thromb Vasc Biol 28:2016-2022.
121. van Herk T, Brussee J, van den Nieuwendijk AM, van der Klein PA, IJzerman AP, Stannek C, Burmeister, and Lorenzen A (2003) Pyrazole derivatives as partial agonists for the nicotinic acid receptor. J Med Chem 46:3945-3951.
122. Walters RW, Shukla AK, Kovacs JJ, Violin JD, DeWire SM, Lam CM, Chen JR, Muehlbauer MJ, Whalen EJ, and Lefkowitz RJ (2009) beta-Arrestin1 mediates nicotinic acidinduced flushing, but not its antilipolytic effect, in mice. J Clin Invest 119:1312-1321.
123. Warne T, Serrano-Vega MJ, Baker JG, Moukhametzianov R, Edwards PC, Henderson R, Leslie AG, Tate CG, and Schertler GF (2008) Structure of a beta1- adrenergic G-protein-coupled receptor. Nature 454:486-491.
124. Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, et al. (2003) Molecular identification of high and low affinity receptors for nicotinic acid. J Biol Chem 278:9869-9874.
125. Yousefi S, Cooper PR, Mueck B, Potter SL, and Jarai G (2000) cDNA representational difference analysis of human neutrophils stimulated by GM-CSF. Biochem Biophys Res Commun 277:401-409.
126. Zellner C, Pullinger CR, Aouizerat BE, Frost PH, Kwok PY, Malloy MJ, and Kane JP (2005) Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors. Hum Mutat 25:18-21.
127. Zhou L, Tang Y, Cryan EV, and Demarest KT (2007) Human epidermoid A431 cells express functional nicotinic acid receptor HM74a. Mol Cell Biochem 294:243-248.
128. Zingoni A, Rocchi M, Storlazzi CT, Bernardini G, Santoni A, and Napolitano M (1997) Isolation and chromosomal localization of GPR31, a human gene encoding a putative G protein-coupled receptor. Genomics 42:519-523.