Unsaturated fatty acids induce inhibition of the A1-adenosine receptor in rat brain membranes

We examined the effect of fatty acids (FA) and some other bioactive lipids on A1-adenosine receptor (A1-AR) binding in rat brain membranes using the selective agonist (3H)-N6-cyclohexyladenosine [(3H)CHA]. A significant reduction in ligand binding was observed at micromolar concentrations of unsaturated fatty acid with the following potency: oleic < arachidonic < decosaenoic < linoleic < linolenic acid. The other tested compounds: lysophospholipids, platelet-activating factor (PAF) and GM1-ganglioside were without effect on A1-AR expression. The inhibition with unsaturated FA was non-competitive and partially reversed by albumin. The A1-AR agonist binding inhibition evoked by unsaturated FA in many respects is similar to that observed previously following ischaemia and may be contributory to the increased excitability of post-ischaemic brain.