Inhibition of ligand binding to G protein-coupled receptors by arachidonic acid.
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.
Bordayo
Elizabeth Z
EZ
Alzheimer's Research Center, HealthPartners Research Foundation, Saint Paul, MN 55101-2502, USA.
Fawcett
John R
JR
Lagalwar
Sarita
S
Svitak
Aleta L
AL
Frey
William H
WH
D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000737:chemistry / Q000378:metabolism; D004174:Diprenorphine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000737:chemistry / Q000378:metabolism; D019832:N-Methylscopolamine / Q000737:chemistry / Q000378:metabolism; D009292:Narcotic Antagonists / Q000737:chemistry / Q000378:metabolism; D010276:Parasympatholytics / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000737:chemistry / Q000378:metabolism; D011869:Radioligand Assay; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000737:chemistry / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D008024:Ligands; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D010276:Parasympatholytics; D020033:Protein Isoforms; D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled; D011976:Receptors, Muscarinic; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D004174:Diprenorphine; D016718:Arachidonic Acid; D012701:Serotonin; D004082:Dihydroalprenolol; D011813:Quinuclidinyl Benzilate; D019832:N-Methylscopolamine