Kjome J R, Swenson K A, Johnson M N, Bordayo E Z, Anderson L E, Klevan L C, Fraticelli A I, Aldrich S L, Fawcett J R, Venters H D, Ala T A, Frey W H
Department of Neurology, Alzheimer's Treatment and Research Center, HealthPartners, Regions Hospital, St. Paul, MN 55101-2595, USA.
J Mol Neurosci. 1998 Jun;10(3):209-17. doi: 10.1007/BF02761775.
Arachidonic acid (AA) inhibits the binding of [3H]quinclidinyl benzilate ([3H]QNB) to the human brain muscarinic cholinergic receptor (mAChR). AA inhibits at lower concentrations in the absence of glutathione (I50 = 15 microM) than in the presence of glutathione (I50 = 42 microM). Inhibition of mAChR binding shows specificity for AA and is reduced with loss of one or more double bonds or with either a decrease or increase in the length of the fatty acid chain. Metabolism of AA by the lipoxygenase, epoxygenase, or fatty acid cyclooxygenase pathways is not required for the inhibitory activity of AA on mAChR binding. Inhibition of [3H]QNB binding by AA is reversible. While decreasing Bmax, AA increased the apparent KD for [3H]QNB and for the more polar antagonist [3H]NMS. In addition, AA inhibits binding of the agonist [3H]oxotremorine-M (I50 = 60 microM) and is the first mediator of mAChR action to be shown to reversibly inhibit mAChR binding. The feedback inhibition of the mAChR by AA may serve a homeostatic function similar to the reuptake and hydrolysis of acetylcholine following cholinergic nerve transmission.
花生四烯酸（AA）抑制[3H]喹硫平（[3H]QNB）与人脑毒蕈碱胆碱能受体（mAChR）的结合。与存在谷胱甘肽时相比（I50 = 42 microM），AA在无谷胱甘肽时以较低浓度发挥抑制作用（I50 = 15 microM）。mAChR结合的抑制对AA具有特异性，并且随着一个或多个双键的缺失或脂肪酸链长度的减少或增加而减弱。AA对mAChR结合的抑制活性不需要通过脂氧合酶、环氧合酶或脂肪酸环氧化酶途径对AA进行代谢。AA对[3H]QNB结合的抑制是可逆的。在降低Bmax的同时，AA增加了[3H]QNB以及极性更强的拮抗剂[3H]NMS的表观解离常数（KD）。此外，AA抑制激动剂[3H]氧化震颤素-M的结合（I50 = 60 microM），并且是首个被证明可可逆抑制mAChR结合的mAChR作用介质。AA对mAChR的反馈抑制可能起到类似于胆碱能神经传递后乙酰胆碱再摄取和水解的稳态功能。
