Molecular identification of high and low affinity receptors for nicotinic acid.

Article Details

Citation

Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB

Molecular identification of high and low affinity receptors for nicotinic acid.

J Biol Chem. 2003 Mar 14;278(11):9869-74. Epub 2003 Jan 9.

PubMed ID
12522134 [ View in PubMed
]
Abstract

Nicotinic acid has been used clinically for over 40 years in the treatment of dyslipidemia producing a desirable normalization of a range of cardiovascular risk factors, including a marked elevation of high density lipoprotein and a reduction in mortality. The precise mechanism of action of nicotinic acid is unknown, although it is believed that activation of a G(i)-G protein-coupled receptor may contribute. Utilizing available information on the tissue distribution of nicotinic acid receptors, we identified candidate orphan receptors. The selected orphan receptors were screened for responses to nicotinic acid, in an assay for activation of G(i)-G proteins. Here we describe the identification of the G protein-coupled receptor HM74 as a low affinity receptor for nicotinic acid. We then describe the subsequent identification of HM74A in follow-up bioinformatics searches and demonstrate that it acts as a high affinity receptor for nicotinic acid and other compounds with related pharmacology. The discovery of HM74A as a molecular target for nicotinic acid may facilitate the discovery of superior drug molecules to treat dyslipidemia.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Inositol nicotinateHydroxycarboxylic acid receptor 2ProteinHumans
Yes
Agonist
Details
Inositol nicotinateHydroxycarboxylic acid receptor 3ProteinHumans
Yes
Agonist
Details
NiacinHydroxycarboxylic acid receptor 2ProteinHumans
Yes
Agonist
Details
NiacinHydroxycarboxylic acid receptor 3ProteinHumans
Yes
Agonist
Details
Polypeptides
NameUniProt ID
Hydroxycarboxylic acid receptor 2Q8TDS4Details
Hydroxycarboxylic acid receptor 3P49019Details