Potentiation of human α4β2 neuronal nicotinic receptors by a Flustra foliacea metabolite
Section snippets
Acknowledgements
We thank Dr. Jon Lindstrom for providing all the human nicotinic receptor subunits DNAs. This work was supported by grants CTIDIB/2002/138 and GRUPOS03/038 from Generalitat Valenciana, grants BMC2002-0097 (M.C.), PM1998-0097 (F.S.) and SAF2002-00209 (S.S.) from the Ministry of Education of Spain, a predoctoral fellowship from Generalitat Valenciana (L.M.V), and a Fulbright Grant (K.P.R).
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2017, Journal of Biological ChemistryCitation Excerpt :We express (α4)3(β2)2 nAChR, wild-type or containing amino acid substitutions, in Xenopus laevis oocytes and use two-electrode voltage-clamp recordings to assess the effect of these substitutions on (α4)3(β2)2 nAChR modulation by CMPI, NS9283 (3-[3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl]benzonitrile, another PAM that also requires the presence of α4:α4 interface for potentiation; Refs. 17 and 32), and desformylflustrabromine (dFBr, a PAM of (α4)3(β2)2 and (α4)2(β2)3 nAChRs (33, 34)). Previous studies have established dFBr, CMPI, and NS9283 as potent nAChR PAMs with high selectivity for the α4-containing nAChRs (28, 31, 35). In addition, the effects of dFBr, CMPI and NS9283 on high- and low-agonist sensitivity isoforms of α4β2 nAChR have been examined by recording ACh-induced currents from Xenopus oocytes injected with α4 and β2 subunits RNAs at ratios that favor the expression of (α4)3(β2)2 or (α4)2(β2)3 nAChR.
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2017, Journal of Biological Chemistry