Facilitation by arachidonic acid of acetylcholine release from the rat hippocampus

We investigated the effect of arachidonic acid (AA) on the release of [H-3]acetylcholine ([H-3]ACh) from the rat hippocampus. AA (3-30 mu M) increased the basal tritium outflow and the field-electrically evoked release of [H-3]ACh from hippocampal slices in a concentration-dependent manner. AA (30 mu M) produced a 69 +/- 7% facilitation of the evoked and a 36 +/- 3% facilitation of basal tritium outflow. The effect of AA (30 mu M) on the evoked tritium release was prevented by bovine serum albumin(BSA, 1%), which quenches AA, and was unaffected by the cyclooxygenase inhibitor, indomethacin (100 mu M), and the lipooxygenase inhibitor, nordihydroguaiaretic acid (50 mu M). Phospholipase A(2) (PLA(2), 2 U/ml), an enzyme that releases AA from the sn-2 position of phospholipids, mimicked the facilitatory effect of AA on the evoked tritium release (86 +/- 14% facilitation), an effect prevented by BSA (1%). The PLA(2) activator, melittin (1 mu M), enhanced the evoked tritium release by 98 +/- 11%, an effect prevented by the PLA(2) inhibitor, arachidonyl trifluromethylketone (AACOCF(3), 20 mu M), and by BSA (1%). AA (30 mu M), but not arachidic acid (30 mu M), also facilitated (72 +/- 9%) the veratridine (10 mu M)-evoked [H-3]ACh release from superfused hippocampal synaptosomes, whereas PLA(2) (2 U/ml) and melittin (1 mu M) caused a lower facilitation (46 +/- 1% and 38 +/- 5%, respectively). The present results show that both exogenously added and endogenously produced AA increase the evoked release of [H-3]ACh from rat hippocampal nerve terminals. Since muscarinic activation triggers AA production and we now observed that AA enhances ACh release, it is proposed that AA may act as a facilitatory retrograde messenger in hippocampal cholinergic muscarinic transmission as it has been proposed to act in glutamatergic transmission. (C) 1999 Elsevier Science B.V. All rights reserved.