Facilitation by arachidonic acid of acetylcholine release from the rat hippocampus.
We investigated the effect of arachidonic acid (AA) on the release of [3H]acetylcholine ([3H]ACh) from the rat hippocampus. AA (3-30 microM) increased the basal tritium outflow and the field-electrically evoked release of [3H]ACh from hippocampal slices in a concentration-dependent manner. AA (30 microM) produced a 69+/-7% facilitation of the evoked and a 36+/-3% facilitation of basal tritium outflow. The effect of AA (30 microM) 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 microM), and the lipooxygenase inhibitor, nordihydroguaiaretic acid (50 microM). Phospholipase A2 (PLA2, 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 PLA2 activator, melittin (1 microM), enhanced the evoked tritium release by 98+/-11%, an effect prevented by the PLA2 inhibitor, arachidonyl trifluromethylketone (AACOCF3, 20 microM), and by BSA (1%). AA (30 microM), but not arachidic acid (30 microM), also facilitated (72+/-9%) the veratridine (10 microM)-evoked [3H]ACh release from superfused hippocampal synaptosomes, whereas PLA2 (2 U/ml) and melittin (1 microM) 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 [3H]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.
Almeida
T
T
Laboratory of Neurosciences, Faculty of Medicine, University of Lisbon, Av. Prof. Egas Moniz, 1649-035, Lisbon, Portugal.
Cunha
R A
RA
Ribeiro
J A
JA
D000109:Acetylcholine / Q000493:pharmacokinetics*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004537:Eicosanoic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D008555:Melitten / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000493:pharmacokinetics*; D009924:Organ Culture Techniques; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium; D014665:Vasodilator Agents / Q000493:pharmacokinetics*
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D004537:Eicosanoic Acids; D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D014665:Vasodilator Agents; C081565:arachidonyltrifluoromethane; D014316:Tritium; D008555:Melitten; D016718:Arachidonic Acid; D009637:Masoprocol; D010741:Phospholipases A; D054467:Phospholipases A2; D000109:Acetylcholine; C094477:arachidic acid; D007213:Indomethacin