Abstract
The synthetic α-conotoxin Vc1.1 is a small disulfide bonded peptide currently in development as a treatment for neuropathic pain. Unlike Vc1.1, the native post-translationally modified peptide vc1a does not act as an analgesic in vivo in rat models of neuropathic pain. It has recently been proposed that the primary target of Vc1.1 is the α9α10 nicotinic acetylcholine receptor (nAChR). We show that Vc1.1 and its post-translationally modified analogs vc1a, [P6O]Vc1.1, and [E14γ]Vc1.1 are equally potent at inhibiting ACh-evoked currents mediated by α9α10 nAChRs. This suggests that α9α10 nAChRs are unlikely to be the molecular mechanism or therapeutic target of Vc1.1 for the treatment of neuropathic pain.
Footnotes
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This work was supported by funding from the Australian Research Council (DP0208295) and National Health and Medical Research Council (NHMRC) (352446). M.J.C. is an NHMRC Senior Principal Research Fellow. D.J.C. is an Australian Research Council Professorial Fellow.
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S.T.N. and R.J.C. contributed equally to this work.
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Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
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doi:10.1124/mol.107.040568.
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ABBREVIATIONS: nAChR, nicotinic acetylcholine receptor; MS, mass spectrometry; HF, hydrogen fluoride; TFA, trifluoroacetic acid; RP-HPLC, reversed-phase–high-performance liquid chromatography; ES-MS, electrospray-mass spectrometry; ACh, acetylcholine; PNL, partial ligation of the left sciatic nerve; PWT, paw withdrawal threshold; AChBP, acetylcholine binding protein.
- Received August 3, 2007.
- Accepted September 5, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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