Nicotine exerts a permissive role on NMDA receptor function in hippocampal noradrenergic terminals.
The coexistence of nicotinic cholinergic receptors (nAChRs) and of N-methyl-D-aspartate (NMDA) receptors on the same noradrenergic axon terminals and the nAChR/NMDA receptor cross-talk were investigated by monitoring the release of noradrenaline (NA) evoked in superfused rat hippocampal synaptosomes by (-)-nicotine and NMDA alone or in combination. In medium containing a physiological concentration (1.2 mM) of Mg2+, the release of [3H]NA was very slightly increased by NMDA plus glycine, whereas it was significantly enhanced by (-)-nicotine. The (-)-nicotine/NMDA combination elicited supraadditive release which was totally abolished by the nAChR blocker mecamylamine and partly prevented by selectively blocking NMDA receptors. Supraadditive [3H]NA release was also observed by exposing synaptosomes to veratrine, but not to ionomycin. The supraadditive release elicited by the (-)-nicotine/NMDA or the veratrine/NMDA combination was sensitive to the protein kinase A/C inhibitor staurosporine and the selective protein kinase A inhibitor H89, but insensitive to the protein kinase C inhibitor Ro 31-8220. It is concluded that (i) release-modulating nAChRs and NMDA receptors coexist on hippocampal noradrenergic axon terminals; and (ii) nicotine permits NMDA receptor activation in the presence of Mg2+, possibly because the nicotine-induced influx of Na+ depolarizes the nerve ending membrane sufficiently to remove the Mg2+ block.
Risso
Francesca
F
Sezione di Farmacologia e Tossicologia, Dipartimento di Medicina Sperimentale, Università di Genova, Viale Cembrano 4, 16148 Genoa, Italy.
Grilli
Massimo
M
Parodi
Monica
M
Bado
Marcella
M
Raiteri
Maurizio
M
Marchi
Mario
M
D000818:Animals; D002118:Calcium / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; C053672:selfotel; D016202:N-Methylaspartate; D008464:Mecamylamine; D016291:Dizocilpine Maleate; D009538:Nicotine; D002118:Calcium