HCA2 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 HCA2 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. At high doses, niacin produces marked anti-inflammatory effects in a variety of tissues – including the brain, gastrointestinal tract, skin, and vascular tissue – through activation of HCA2. Niacin has also been shown to attenuate neuroinflammation in part through NIACR1 binding; consequently, HCA2 has been identified as a potential therapeutic target for treating neuroimmune disorders such as multiple sclerosis and Parkinson's disease. The precise mechanism of action of niacin therapeutic effects has not been fully elucidated, but appears to work in part through activation of HCA2 which reduces the levels of intracellular cAMP thereby inhibiting lipolysis in adipocytes. In contrast, the flushing effect is due to HCA2 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.
Hydroxycarboxylic acid receptor 2
Growth hormone secretagogue receptor
Norepinephrine transporter
Prolactin-releasing peptide receptor
G protein-coupled receptor kinase 3
Thiamine transporter 1
Tropomyosin receptor kinase A
Prostaglandin-endoperoxide synthase 2