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Article Dans Une Revue Biochemical Pharmacology Année : 2015

α-conotoxin MrIC is a biased agonist at α7 nicotinic acetylcholine receptors

Alexander Mueller
  • Fonction : Auteur
Hana Starobova
  • Fonction : Auteur
Marco C Inserra
  • Fonction : Auteur
Jennifer R Deuis
  • Fonction : Auteur
Richard J Lewis
  • Fonction : Auteur
Paul F Alewood
  • Fonction : Auteur
Norelle L Daly
  • Fonction : Auteur
Irina Vetter

Résumé

MrIC is a recently described selective agonist of endogenously expressed α7 nAChR. In this study, we further characterize the pharmacological activity of MrIC using Ca(2+) imaging approaches in SH-SY5Y cells endogenously expressing α7 nAChR and demonstrate that MrIC exclusively activates α7 nAChR modulated by type II positive allosteric modulators, including PNU120596. MrIC was a full agonist at PNU120596-modulated α7 nAChR compared with choline, albeit with slower kinetics, but failed to elicit a Ca(2+) response in the absence of PNU120596. Interestingly, the NMR structure of MrIC showed a typical 4/7 α-conotoxin fold, indicating that its unusual pharmacological activity is likely sequence-dependent. Overall, our results suggest that MrIC acts as a biased agonist that can only activate α7 nAChR modified by type II positive allosteric modulators, and thus represents a valuable tool to probe the pharmacological properties of this important ion channel.
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Dates et versions

hal-02306979 , version 1 (08-10-2019)

Identifiants

Citer

Alexander Mueller, Hana Starobova, Marco C Inserra, Ai-Hua Jin, Jennifer R Deuis, et al.. α-conotoxin MrIC is a biased agonist at α7 nicotinic acetylcholine receptors. Biochemical Pharmacology, 2015, 94 (2), pp.155-163. ⟨10.1016/j.bcp.2015.01.011⟩. ⟨hal-02306979⟩
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