TY - JOUR T1 - Characterization of a G Protein-Coupled Receptor for Nicotinic Acid JF - Molecular Pharmacology JO - Mol Pharmacol SP - 349 LP - 357 DO - 10.1124/mol.59.2.349 VL - 59 IS - 2 AU - Anna Lorenzen AU - Christina Stannek AU - Heidrun Lang AU - Viktor Andrianov AU - Ivars Kalvinsh AU - Ulrich Schwabe Y1 - 2001/02/01 UR - http://molpharm.aspetjournals.org/content/59/2/349.abstract N2 - Nicotinic acid is a lipid-lowering agent widely used to treat hypertriglyceridemia and to elevate low high density lipoprotein levels. However, the underlying mechanisms are poorly understood. In this study, G protein activation by nicotinic acid and derivatives was assessed as stimulation of guanosine 5′-(γ-[35S]-thio)triphosphate ([35S]GTPγS) binding, and [3H]nicotinic acid was used for specific labeling of binding sites. Nicotinic acid (EC50 ∼1 μM) stimulated [35S]GTPγS binding in membranes from rat adipocytes and spleen, but not from other tissues. G protein activation in adipocyte membranes in the presence of maximally activating concentrations of the selective A1adenosine receptor agonist 2-chloro-N 6-cyclopentyladenosine and nicotinic acid was almost additive, indicating that G proteins of mostly distinct pools were activated by these agonists. G protein activation by nicotinic acid and related substances in spleen and adipocytes revealed identical pharmacological profiles. [3H]Nicotinic acid specifically detected guanine nucleotide-sensitive binding sites of identical pharmacology in adipocyte and spleen membranes. The site of action of nicotinic acid is distinct from other G protein-coupled receptors. These data indicate that nicotinic acid most probably acts on a specific G protein-coupled receptor. ER -