Characterization of a G protein-coupled receptor for nicotinic acid
| Autor: | Heidrun Lang, Christina Stannek, Anna Lorenzen, Viktor Andrianov, Ivars Kalvinsh, Ulrich Schwabe |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
G protein GTPgammaS Receptors Cell Surface In Vitro Techniques Receptors Nicotinic Sulfur Radioisotopes Tritium Niacin GTP Phosphohydrolases chemistry.chemical_compound Structure-Activity Relationship Ganglion type nicotinic receptor GTP-Binding Proteins Adipocytes Animals Rats Wistar Receptor G protein-coupled receptor Hypolipidemic Agents Pharmacology Binding Sites Chemistry Adenosine receptor Rats Nicotinic agonist Biochemistry Guanosine 5'-O-(3-Thiotriphosphate) Pyrazines Adenylyl Cyclase Inhibitors Molecular Medicine Alpha-4 beta-2 nicotinic receptor Spleen |
| Zdroj: | Molecular pharmacology. 59(2) |
| ISSN: | 0026-895X |
| Popis: | 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'-(gamma-[(35)S]-thio)triphosphate ([(35)S]GTPgammaS) binding, and [(3)H]nicotinic acid was used for specific labeling of binding sites. Nicotinic acid (EC(50) approximately 1 microM) stimulated [(35)S]GTPgammaS 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 A(1) adenosine 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. [(3)H]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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|