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• W1989059619 abstract "Background and purpose: Two metabolites of tryptophan, 5‐hydroxyindole and kynurenic acid (kynurenate) affect the function of α7 nicotinic acetylcholine receptors (nAChRs), as measured by electrophysiological and Ca 2+ fluorescence techniques. To better understand the modulations by 5‐hydroxyindole and kynurenate of the function of nAChR subtypes, we compared the effects of 5‐hydroxyindole and kynurenate on the release of various transmitters evoked by nAChR activation. Experimental approach: The function of α7nAChRs located on glutamatergic terminals was investigated by monitoring the release of [ 3 H]D‐aspartate or of endogenous glutamate from neocortical synaptosomes. We also comparatively considered non‐α7 release‐enhancing nAChRs localized on hippocampal noradrenergic or cholinergic terminals, as well as on striatal dopaminergic terminals. Key results: Epibatidine or nicotine, inactive on their own on basal release, enhanced [ 3 H]D‐ aspartate and glutamate efflux in presence of 5‐hydroxyindole. The release evoked by nicotine plus 5‐hydroxyindole was abolished by methyllycaconitine or α‐bungarotoxin. Presynaptic nAChRs mediating the release of [ 3 H]noradrenaline ([ 3 H]NA), [ 3 H]dopamine ([ 3 H]DA), or [ 3 H]ACh were inhibited by 5‐OHi. The α7nAChR‐mediated release of [ 3 H]D‐aspartate was reduced by kynurenate at concentrations unable to affect the non‐α7 receptor‐mediated release of tritiated NA, DA or ACh. Conclusions and Implications: (i) 5‐hydroxyindole permits selective activation of α7nAChRs mediating glutamate release; (ii) kynurenate down‐regulates the permissive role of 5‐hydroxyindole on α7nAChR activation; (iii) the non‐α7nAChRs mediating release of NA, DA or ACh can be inhibited by 5‐hydroxyindole, but not by kynurenate. These findings suggest up the possibility of developing novel drugs able to modulate selectively the cholinergic‐glutamatergic transmission. British Journal of Pharmacology (2006) 149 , 724–732. doi: 10.1038/sj.bjp.0706914" @default.
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• W1989059619 date "2006-11-01" @default.
• W1989059619 modified "2023-10-17" @default.
• W1989059619 title "Modulation of the function of presynaptic <i>α</i> 7 and non-<i>α</i> 7 nicotinic receptors by the tryptophan metabolites, 5-hydroxyindole and kynurenate in mouse brain" @default.
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• W1989059619 doi "https://doi.org/10.1038/sj.bjp.0706914" @default.
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