Molecular identification of nicotinic acid receptor

Biochem Biophys Res Commun. 2003 Mar 28;303(1):364-9. doi: 10.1016/s0006-291x(03)00342-5.


Nicotinic acid and its derivative, Acipimox, have been widely used in the treatment of hyperlipidemia. Pharmacological studies have demonstrated that they exert the beneficial effect through the activation of a Gi-protein-coupled receptor on adipocyte, which has remained elusive to date. Here we show that a novel GPCR, designated HM74b because of its high similarity to HM74, is a receptor for nicotinic acid. HM74b mRNA is found in human, murine, and rat adipose tissues. Nicotinic acid and Acipimox inhibit forskolin-stimulated intracellular cAMP accumulation in human HM74b-expressing cells and activate GTP gamma S binding in a dose-dependent manner. [3H]Nicotinic acid specifically binds to HM74b-expressing membrane and its binding is replaced by Acipimox. This finding will open a new phase of research on the physiological role of nicotinic acid and will be a clue to develop novel antihyperlipidemic drugs.

MeSH terms

  • Adipocytes / metabolism
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cloning, Molecular
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Humans
  • Mice
  • Molecular Sequence Data
  • Niacin / pharmacology
  • Open Reading Frames
  • Poly A
  • Pyrazines / chemistry*
  • RNA, Messenger / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Nicotinic / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Tissue Distribution


  • DNA, Complementary
  • Pyrazines
  • RNA, Messenger
  • Receptors, Nicotinic
  • Colforsin
  • Poly A
  • Niacin
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Cyclic AMP
  • acipimox