title: Chronic nicotine exposure selectively activates a carrier-mediated release of endogenous glutamate and aspartate from rat hippocampal synaptosomes.
abstract: The effect of chronic nicotine treatment on the release of endogenous glutamate (GLU), aspartate (ASP) and GABA evoked in vitro by KCl, 4-aminopyridine (4AP) and nicotinic agonists in synaptosomes of rat hippocampus was investigated. Rats were chronically administered with nicotine bitartrate or saline vehicle each for 14 days using osmotic mini-pumps. Hippocampal synaptosomes were stimulated with KCl, 4AP, nicotine or with choline (Ch) and 5-iodo-A-85380 dihydrochloride (5IA85380). The GLU and ASP overflow evoked by Ch, nicotine, KCl and 4AP were increased in treated animals while the nicotine-evoked GABA overflow was reduced and that evoked by Ch, KCl and 4AP was unaffected. The 5IA85380-evoked overflow of the three aminoacids (AAs) was always reduced. The increase of ASP and GLU overflow evoked by KCl, 4AP or Ch was blocked by dl-threo-β-benzyloxyaspartic acid (dl-TBOA), a carrier transporter inhibitor, and by inhibitors of the Na(+)/Ca(2+) exchangers 2-[[4-[(4-nitrophenyl)methoxy]phenyl]methyl]-4-thiazolidinecarboxylic acid ethyl ester (SN-6) and 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea mesylate (KB-R7943). In conclusion long-term nicotine treatment may selectively increase GLU and ASP overflow elicited by KCl, 4AP and Ch through the activation of a carrier-mediated release mechanism and completely abolished the stimulatory effects of α4β2 nAChRs which modulate the release of all the three AA.
authors.affiliation: Section of Pharmacology and Toxicology, Department of Experimental Medicine, University of Genoa, Genoa, Italy. marchi@pharmatox.unige.it
authors.forename: Mario
authors.initials: M
authors.lastname: Marchi
authors.forename: Stefania
authors.initials: S
authors.lastname: Zappettini
authors.forename: Guendalina
authors.initials: G
authors.lastname: Olivero
authors.forename: Anna
authors.initials: A
authors.lastname: Pittaluga
authors.forename: Massimo
authors.initials: M
authors.lastname: Grilli
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002352:Carrier Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D004334:Drug Administration Schedule; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018722:Nicotinic Agonists; D001224:Aspartic Acid; D018698:Glutamic Acid; D009538:Nicotine