Inhibition of ligand binding to G protein-coupled receptors by arachidonic acid

• Published in: Journal of molecular neuroscience Vol. 27; no. 2; pp. 185 - 194
• Main Authors: Bordayo, Elizabeth Z, Fawcett, John R, Lagalwar, Sarita, Svitak, Aleta L, Frey, Jr, William H
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.01.2005
• Subjects: Adrenergic beta-Antagonists - chemistry; Adrenergic beta-Antagonists - metabolism; Animals; Arachidonic Acid - chemistry; Arachidonic Acid - metabolism; Dihydroalprenolol - chemistry; Dihydroalprenolol - metabolism; Diprenorphine - chemistry; Diprenorphine - metabolism; Humans; Ligands; Molecular Structure; Muscarinic Antagonists - chemistry; Muscarinic Antagonists - metabolism; N-Methylscopolamine - chemistry; N-Methylscopolamine - metabolism; Narcotic Antagonists - chemistry; Narcotic Antagonists - metabolism; Nicotine; Parasympatholytics - chemistry; Parasympatholytics - metabolism; Protein Binding; Protein Isoforms - metabolism; Proteins; Quinuclidinyl Benzilate - chemistry; Quinuclidinyl Benzilate - metabolism; Radioligand Assay; Receptors, Adrenergic, beta-2 - metabolism; Receptors, G-Protein-Coupled - metabolism; Receptors, Muscarinic - metabolism; Receptors, Opioid, mu - metabolism; Receptors, Serotonin - metabolism; Serotonin - chemistry; Serotonin - metabolism
• ISSN: 0895-8696; 0895-8696; 1559-1166
• DOI: 10.1385/JMN:27:2:185

Arachidonic acid (AA), released in response to muscarinic acetylcholine receptor (mAChR) stimulation, previously has been reported to function as a reversible feedback inhibitor of the mAChR. To determine if the effects of AA on binding to the mAChR are subtype specific and whether AA inhibits ligand binding to other G protein-coupled receptors (GPCRs), the effects of AA on ligand binding to the mAChR subtypes (M1, M2, M3, M4, and M5) and to the micro-opioid receptor, beta2-adrenergic receptor (beta2-AR), 5-hydroxytryptamine receptor (5-HTR), and nicotinic receptors were examined. AA was found to inhibit ligand binding to all mAChR subtypes, to the beta2-AR, the 5-HTR, and to the micro-opioid receptor. However, AA does not inhibit ligand binding to the nicotinic receptor, even at high concentrations of AA. Thus, AA inhibits several types of GPCRs, with 50% inhibition occurring at 3-25 MuM, whereas the nicotinic receptor, a non-GPCR, remains unaffected. Further research is needed to determine the mechanism by which AA inhibits GPCR function.