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 m u M) produced a 69 +/- 7% facilitation of the evoked and a 36 +/- 3% facili tation of basal tritium outflow. The effect of AA (30 mu M) on the evoked t ritium release was prevented by bovine serum albumin(BSA, 1%), which quench es AA, and was unaffected by the cyclooxygenase inhibitor, indomethacin (10 0 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 th e 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 t ritium 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%) t he veratridine (10 mu M)-evoked [H-3]ACh release from superfused hippocampa l synaptosomes, whereas PLA(2) (2 U/ml) and melittin (1 mu M) caused a lowe r 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 mus carinic activation triggers AA production and we now observed that AA enhan ces ACh release, it is proposed that AA may act as a facilitatory retrograd e messenger in hippocampal cholinergic muscarinic transmission as it has be en proposed to act in glutamatergic transmission. (C) 1999 Elsevier Science B.V. All rights reserved.