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  • Title: Inactivation of muscarinic acetylcholine receptors in brain synaptic membranes by free fatty acids. Evaluation of the role of lipid phase.
    Author: Okun IM, Merezhinskaya NV, Rakovich AA, Volkovets TM, Aksentsev SL, Konev SV.
    Journal: Gen Physiol Biophys; 1986 Jun; 5(3):243-58. PubMed ID: 3758660.
    Abstract:
    Arachidonic, linolenic and linoleic acids decreased the binding of the m-cholinergic antagonist [3H] QNB and did not affect the ratio of high to low affinity binding sites to the agonist carbamoylcholine in rat brain synaptic membranes. In the presence of arachidonic acid, SH-reagent N-ethylmaleimide acquired the ability to block QNB binding to receptor. Lipids in the bilayer and annular regions were probed by fluorescence of 1,6-diphenyl-1, 3, 5-hexatriene and pyrene. A microviscosity drop induced by increasing temperature from 10 to 37 degrees C did not affect the level of QNB equilibrium binding, whereas arachidonic acid strongly inhibited the binding at concentrations inducing the same drop in microviscosity as that induced by heating. For various unsaturated fatty acids an equal extent of receptor blocking was reached at quite different degrees of bilayer fluidization, the state of annular lipid being not changed under these conditions. It is suggested that the effect of unsaturated acids is reached through their direct interaction with the receptor, which undergoes a conformational change, rather than by an alteration of the physical state of the lipid phase of the membrane.
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