title: Nicotine has a permissive role on the activation of metabotropic glutamate 5 receptors coexisting with nicotinic receptors on rat hippocampal noradrenergic nerve terminals.
abstract: The existence of metabotropic glutamate receptors (mGluRs) on hippocampal noradrenergic nerve terminals and their interaction with coexisting nicotinic acetylcholine receptors (nAChRs) were investigated in superfused rat synaptosomes using [(3)H]-noradrenaline ([(3)H]-NA) release as a readout. The selective agonist of group I mGluRs, (S)-3,5-dihydroxyphenylglycine (DHPG), inactive on its own, acquired ability to release [(3)H]-NA when added together with (-)-nicotine. The effect of DHPG was prevented by 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective antagonist of mGluR5, but not by 7-(hydroxyimino)cyclopropane[b]chromen-1-carboxylate ethyl ester (CPCCOEt), selective antagonist of mGluR1. The [(3)H]-NA release evoked by (-)-nicotine plus DHPG was totally abrogated by the nAChR antagonist mecamylamine. Veratrine mimicked the permissive role of (-)-nicotine on the activation of mGluR5 mediating [(3)H]-NA release. The mGluR5-mediated component of the [(3)H]-NA release provoked by DHPG plus (-)-nicotine was blocked by xestospongin C, a selective antagonist of inositoltrisphosphate (IP(3)) receptors. It can be concluded that (i) release-enhancing mGluRs of subtype 5 exist on hippocampal noradrenergic axon terminals; (ii) activation of mGluR5 to mediate IP(3)-dependent NA release requires activation of depolarizing nAChRs coexisting on the same terminals.
authors.affiliation: Sezione di Farmacologia e Tossicologia, Dipartimento di Medicina Sperimentale, Università di Genova, 16148 Genova, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Parodi
authors.forename: Laura
authors.initials: L
authors.lastname: Patti
authors.forename: Massimo
authors.initials: M
authors.lastname: Grilli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Raiteri
authors.forename: Mario
authors.initials: M
authors.lastname: Marchi
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*
chemical_list: D018094:Receptors, Metabotropic Glutamate; D009538:Nicotine; D009638:Norepinephrine