Characterization of a G protein-coupled receptor for nicotinic acid

Nicotinic acid is a lipid-lowering agent widely used to treat hypertriglyce ridemia and to elevate low high density lipoprotein levels. However, the un derlying mechanisms are poorly understood. In this study, G protein activat ion by nicotinic acid and derivatives was assessed as stimulation of guanos ine 5'-(gamma-[S-35]-thio)triphosphate ([S-35]GTP gammaS) binding, and [H-3 ]nicotinic acid was used for specific labeling of binding sites. Nicotinic acid (EC50 similar to1 muM) stimulated [S-35]GTP gammaS binding in membrane s from rat adipocytes and spleen, but not from other tissues. G protein act ivation in adipocyte membranes in the presence of maximally activating conc entrations of the selective A(1) adenosine receptor agonist 2-chloro-N-6-cy clopentyl-adenosine and nicotinic acid was almost additive, indicating that G proteins of mostly distinct pools were activated by these agonists. G pr otein activation by nicotinic acid and related substances in spleen and adi pocytes revealed identical pharmacological profiles. [H-3]Nicotinic acid sp ecifically detected guanine nucleotide-sensitive binding sites of identical pharmacology in adipocyte and spleen membranes. The site of action of nico tinic acid is distinct from other G protein-coupled receptors. These data i ndicate that nicotinic acid most probably acts on a specific G protein-coup led receptor.