PT  - JOURNAL ARTICLE
AU  - Philippe Marin
AU  - Brigitte Hamon
AU  - Jacques Glowinski
AU  - Joël Prémont
TI  - Nicotine-Induced Inhibition of Neuronal Phospholipase A2
DP  - 1997 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1277--1283
VI  - 280
IP  - 3
4099  - http://jpet.aspetjournals.org/content/280/3/1277.short
4100  - http://jpet.aspetjournals.org/content/280/3/1277.full
SO  - J Pharmacol Exp Ther1997 Mar 01; 280
AB  - A protective effect of nicotine against glutamate-induced neurotoxicity has previously been reported in cultured striatal and cortical neurons. The aim of this study was to investigate whether nicotine also inhibits glutamate-evoked arachidonic acid release from cultured striatal neurons. (−)-Nicotine selectively inhibited the release of [3H]-arachidonic acid induced by the joint stimulation of α-amino-3-isoxazol-5-propionic acid and metabotropic receptors, whereas the response evoked by the sole activation of N-methyl-d-aspartate receptors remained unchanged. The inhibitory effect of (−)-nicotine was not mediated by nicotinic receptors because it was neither reproduced by acetylcholine (in the presence of atropine) or 1,1-dimethyl-4-phenyl piperazinium, nor reversed by dihydro-β-erythroidine or hexamethonium, two central nicotinic receptor antagonists. (−)-Nicotine, which induced rapidly desensitizing inward currents in 17% of striatal neurons, did not alter the α-amino-3-isoxazol-5-propionic acid-evoked currents. Moreover, (−)-nicotine did not inhibit the accumulation of inositol phosphate derivatives induced by agonists of glutamate metabotropic receptors. In fact, using the fluorogenic phospholipase A2 substrate 1,2-bis-(1-pyrenedecanoyl)-sn-glycero-3-phosphocholine, (−)-nicotine was found to inhibit both particulate and soluble phospholipase A2 activities from striatal neurons. Therefore, (−)-nicotine can modulate a neuronal response (arachidonic acid release) evoked by glutamate but this process is not involved in the neuroprotective effect of the drug on glutamate-induced neurotoxicity. The American Society for Pharmacology and Experimental Therapeutics