TAILIEUCHUNG - Báo cáo khoa học: a-Conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes

Cone snails comprise 500 species of venomous molluscs, which have evolved the ability to generate multiple toxins with varied and often exquisite selectivity. One class, the a-conotoxins, is proving to be a powerful tool for the differentiation of nicotinic acetylcholine receptors (nAChRs). These comprise a large family of complex subtypes, whose significance in physiological functions and pathological conditions is increasingly becoming apparent. After a short introduction into the structure and diversity of nAChRs, this overview summarizes the identification and characterization ofa-conotoxins with selectivity for neur | Eur. J. Biochem. 271 2305-2319 2004 FEBS 2004 doi MINIREVIEW a-Conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes Annette Nicke1 Susan Wonnacott2 and Richard J. Lewis3 Max Planck-Institute for Brain Research Frankfurt Germany department of Biology Biochemistry University of Bath UK 3Institute for Molecular Bioscience University of Queensland Brisbane Australia Cone snails comprise w 500 species of venomous molluscs which have evolved the ability to generate multiple toxins with varied and often exquisite selectivity. One class the a-conotoxins is proving to be a powerful tool for the differentiation of nicotinic acetylcholine receptors nAChRs . These comprise a large family of complex subtypes whose significance in physiological functions and pathological conditions is increasingly becoming apparent. After a short introduction into the structure and diversity of nAChRs this overview summarizes the identification and characterization of a-conotoxins with selectivity for neuronal nAChR subtypes and provides examples of their use in defining the compositions and function of neuronal nAChR subtypes in native vertebrate tissues. Keywords a-conotoxins neuronal nicotinic acetylcholine receptor subtypes pharmacology venom peptides Xenopus oocytes. Neuronal nicotinic acetylcholine receptors The nicotinic acetylcholine receptor family The nicotinic acetylcholine receptor nAChR at the neuromuscular junction was first described as the receptive substance in Langley s historic experiments which lead to the formulation of the receptor concept 1 . nAChRs have been amongst the earliest receptors to be investigated by pharmacological biochemical electrophysiological and molecular biological approaches and to date represent one of the most intensively investigated membrane proteins. While the identification and pharmacological distinction of nAChR subtypes at the neuromuscular .

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