Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2202336 | Neurochemistry International | 2006 | 6 Pages |
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 [3H]-noradrenaline ([3H]-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 [3H]-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 [3H]-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 [3H]-NA release. The mGluR5-mediated component of the [3H]-NA release provoked by DHPG plus (−)-nicotine was blocked by xestospongin C, a selective antagonist of inositoltrisphosphate (IP3) 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 IP3-dependent NA release requires activation of depolarizing nAChRs coexisting on the same terminals.