title: Long-lasting facilitation of 4-amino-n-[2,3-(3)H]butyric acid ([(3)H]GABA) release from rat hippocampal slices by nicotinic receptor activation.
abstract: In this study we explored the effect of the stimulation of nicotinic acetylcholine receptors located on interneurons by measuring 4-amino-n-[2,3-(3)H]butyric acid ([(3)H]GABA) release and monitoring [Ca (2+)](i) in superfused hippocampal slices. In the presence of 6-cyano-7-nitroquinoxaline-2,3-dione, (+/-)-2-amino-5-phosphonopentanoic acid, and atropine, i.e., under the blockade of N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate and muscarinic receptors, nicotine did not alter the spontaneous outflow of [(3)H]GABA, but significantly increased the stimulation-evoked [(3)H]GABA efflux. This effect of nicotine depended on the time interval between nicotine treatment and electrical stimulus, the concentration of nicotine (1-100 microM), and the parameters of electrical depolarization. Acetylcholine (0.03-3 mM), and the alpha 7 subtype-selective agonist choline (0.1-10 mM), also potentiated stimulus-evoked release of [(3)H]GABA, whereas 1,1-dimethyl-4-phenilpiperazinium iodide failed to increase the tritium outflow significantly. The effect of nicotine treatment was prevented by tetrodotoxin (1 microM) and by the nicotinic acetylcholine receptor antagonist mecamylamine (10 microM), and the alpha 7 subtype-selective antagonists alpha-bungarotoxin (100 nM) and methyllycaconitine (10 nM), whereas dihidro-beta-erythroidine (20 nM) was without effect. Perfusion of 100 microM nicotine caused a [Ca(2+)](i) transient in about one-third of the tested interneurons; however, the response to subsequent electrical stimulation remained unchanged. Inhibition of the GABA transporter system by nipecotic acid (1 mM) or by decreasing the bath temperature to 12 degrees C abolished completely the effect of nicotine to potentiate the stimulation-evoked release of GABA. These findings indicate that the activation of alpha 7-type nicotinic receptors of hippocampal interneurons results in a long-lasting ability of these cells to respond to depolarization with an increased release of GABA mediated by the transporter system.
authors.affiliation: Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Köfalvi
authors.forename: B
authors.initials: B
authors.lastname: Sperlágh
authors.forename: T
authors.initials: T
authors.lastname: Zelles
authors.forename: E S
authors.initials: ES
authors.lastname: Vizi
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004357:Drug Synergism; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D026901:Membrane Transport Proteins; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology; D027361:Organic Anion Transporters; D010477:Perfusion; D011392:Proline / Q000031:analogs & derivatives*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*; D026941:Sodium Channel Blockers; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D018118:Chloride Channels; D018691:Excitatory Amino Acid Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; D011978:Receptors, Nicotinic; D026941:Sodium Channel Blockers; D014316:Tritium; C030278:nipecotic acid; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001285:Atropine; D011392:Proline; C010983:homoproline; D011493:Protein Kinase C; D002118:Calcium