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.[1]References
- Facilitation by arachidonic acid of acetylcholine release from the rat hippocampus. Almeida, T., Cunha, R.A., Ribeiro, J.A. Brain Res. (1999) [Pubmed]
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