Bordayo Elizabeth Z, Fawcett John R, Lagalwar Sarita, Svitak Aleta L, Frey William H
Alzheimer's Research Center, HealthPartners Research Foundation, Saint Paul, MN 55101-2502, USA.
J Mol Neurosci. 2005;27(2):185-94. 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.
花生四烯酸（AA）在毒蕈碱型乙酰胆碱受体（mAChR）受到刺激时释放，此前有报道称其作为mAChR的可逆性反馈抑制剂发挥作用。为了确定AA对与mAChR结合的影响是否具有亚型特异性，以及AA是否抑制配体与其他G蛋白偶联受体（GPCR）的结合，研究了AA对配体与mAChR亚型（M1、M2、M3、M4和M5）、微阿片受体、β2 - 肾上腺素能受体（β2 - AR）、5 - 羟色胺受体（5 - HTR）和烟碱样受体结合的影响。发现AA抑制配体与所有mAChR亚型、β2 - AR、5 - HTR和微阿片受体的结合。然而，即使在高浓度的AA下，AA也不抑制配体与烟碱样受体的结合。因此，AA抑制几种类型的GPCR，在3 - 25μM时出现50%的抑制，而烟碱样受体作为一种非GPCR则不受影响。需要进一步研究以确定AA抑制GPCR功能的机制。
