Artículos de revistas
A novel μ-conopeptide, CnIIIC, exerts potent and preferential inhibition of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine receptors
Fecha
2012Registro en:
British Journal of Pharmacology, Volumen 166, Issue 5, 2018, Pages 1654-1668
00071188
14765381
10.1111/j.1476-5381.2012.01837.x
Autor
Favreau, Philippe
Benoit, Evelyne
Hocking, Henry G.
Carlier, Ludovic
D'Hoedt, Dieter
Leipold, Enrico
Markgraf, René
Schlumberger, Sébastien
Córdova, Marco A.
Gaertner, Hubert
Paolini-Bertrand, Marianne
Hartley, Oliver
Tytgat, Jan
Heinemann, Stefan H.
Bert
Institución
Resumen
BACKGROUND AND PURPOSE The μ-conopeptide family is defined by its ability to block voltage-gated sodium channels (VGSCs), a property that can be used for the development of myorelaxants and analgesics. We characterized the pharmacology of a new μ-conopeptide (μ-CnIIIC) on a range of preparations and molecular targets to assess its potential as a myorelaxant. EXPERIMENTAL APPROACH μ-CnIIIC was sequenced, synthesized and characterized by its direct block of elicited twitch tension in mouse skeletal muscle and action potentials in mouse sciatic and pike olfactory nerves. μ-CnIIIC was also studied on HEK-293 cells expressing various rodent VGSCs and also on voltage-gated potassium channels and nicotinic acetylcholine receptors (nAChRs) to assess cross-interactions. Nuclear magnetic resonance (NMR) experiments were carried out for structural data. KEY RESULTS Synthetic μ-CnIIIC decreased twitch tension in mouse hemidiaphragms (IC50= 150 nM), and displayed a higher blocking effect in mouse e