Niacin receptor 1

Niacin receptor 1, also known as NIACR1 or GPR109A, is a protein which in humans is encoded by the NIACR1 gene.

Function

NIACR1 is a high-affinity G_i/G_o-coupled G protein-coupled receptor (GPCR) for nicotinic acid (niacin), and is a member of the nicotinic acid receptor family of GPCRs (the other identified member being Niacin receptor 2, also known as GPR109B). Butyrate is also another common ligand (full agonist) of NIACR1.

Clinical significance

Niacin receptor 1 is an important biomolecular target of niacin which is a widely prescribed drug for the treatment of dyslipidemia and to increase HDL cholesterol but whose therapeutic use is limited by flushing. In NIACR1 knockout mice, the effects of niacin on both lipids and flushing is eliminated. Furthermore, in arrestin beta 1 knockout mice, niacin's effect on flushing is greatly reduced while the lipid modifying effects are maintained.

The precise mechanism of action of niacin therapeutic effects has not been fully elucidated, but appears to work in part through activation of NIACR1 which reduces the levels of intracellular cAMP thereby inhibiting lipolysis in adipocytes. In contrast, the flushing effect is due to NIACR1 activation of ERK 1/2 MAP kinase mediated by arrestin beta 1. Activation of MAP kinase in turn causes release of prostaglandin D2 from Langerhans cells in the skin.