Characterization of a novel ?-conotoxin from conus textile that selectively targets ?6/?3?2?3 nicotinic acetylcholine receptors.

ABSTRACT: ?6?2 Nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic neurons in the CNS are potential therapeutic targets for the treatment of several neuropsychiatric diseases, including nicotine addiction and Parkinson disease. However, recent studies indicate that the ?6 subunit can also associate with the ?4 subunit to form ?6?4 nAChRs that are difficult to pharmacologically distinguish from ?6?2, ?3?4, and ?3?2 subtypes. The current study characterized a novel 16-amino acid ?-conotoxin (?-CTx) TxIB from Conus textile whose sequence is GCCSDPPCRNKHPDLC-amide as deduced from gene cloning. The peptide and an analog with an additional C-terminal glycine were chemically synthesized and tested on rat nAChRs heterologously expressed in Xenopus laevis oocytes. ?-CTx TxIB blocked ?6/?3?2?3 nAChR with an IC(50) of 28 nm. In contrast, the peptide showed little or no block of other tested subtypes at concentrations up to 10 ?m. The three-dimensional solution structure of ?-CTx TxIB was determined using NMR spectroscopy. ?-CTx TxIB represents a uniquely selective ligand for probing the structure and function of ?6?2 nAChRs.

SUBMITTER: Luo S 

PROVIDER: S-EPMC3543038 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature