Titre du document / Document title
5-Hydroxyindole potentiates human α7 nicotinic receptor-mediated responses and enhances acetylcholine-induced glutamate release in cerebellar slices
Auteur(s) / Author(s)
ZWART R. (1) ;
DE FILIPPI G. (1) ;
BROAD L. M. (1) ;
MCPHIE G. I. (1) ;
PEARSON K. H. (1) ;
BALDWINSON T. (1) ;
SHER E. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Eli Lilly and Company Limited, Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey GU20 6PH, ROYAUME-UNI
Résumé / Abstract
The effects of 5-hydroxyindole (5-HI) have been investigated on human a7 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes and GH4 cells, on native a7 nAChRs expressed by IMR-32 cells and on a7 nAChR-mediated events in mossy fibre-granule cell synapses in rat cerebellar slices. In oocytes expressing a7 nAChRs, 5-HI potentiated sub-maximal, 60 μM ACh-induced ion currents in a concentration-dependent manner, the threshold effective concentration being 30 μM. 5-HI itself did not act as an agonist on a7 nAChRs. A maximum potentiation of 12 times the control was observed at 20 mM 5-HI. The effect of I mM 5-HI on the concentration-response curve for ACh revealed that 5-HI increased the potency as well as the eflicacy of ACh on a7 nAChRs. 5-HI also potentiated a7-mediated increases in intracellular free calcium levels in both mammalian cells heterologously expressing human a7 nAChRs and in human IMR-32 neuroblastoma cells expressing native a7 nAChRs. At mossy fibre-granule cell synapses, application of I mM ACh induced glutamate-evoked excitory post-synaptic currents (EPSCs). Co-application of I mM 5-HI with 1 mM ACh further increased the frequency of the EPSCs. The ACh-induced release, as well as the 5-HI-induced enhancement of release, were blocked by 1-10 nM methyllycaconitine or 200 nM α-bungarotoxin, demonstrating that both effects were mediated by presynaptic a7 nAChRs. The results demonstrate that responses mediated by a7 nAChRs are strongly potentiated by 5-HI.
Revue / Journal Title
Neuropharmacology
ISSN
0028-3908
CODEN NEPHBW
Source / Source
2002, vol. 43, n
o3, pp. 374-384 [11 page(s) (article)] (1 p.1/4)
Langue / Language
Anglais
Editeur / Publisher
Elsevier, Kidlington, ROYAUME-UNI
(1970)
(Revue)
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Localisation / Location
INIST-CNRS, Cote INIST : 10408, 35400010655091.0070
Nº notice refdoc (ud4) : 13969357
