RT Journal Article
SR Electronic
T1 Are α9α10 Nicotinic Acetylcholine Receptors a Pain Target for α-Conotoxins?
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1406
OP 1410
DO 10.1124/mol.107.040568
VO 72
IS 6
A1 S. T. Nevin
A1 R. J. Clark
A1 H. Klimis
A1 M. J. Christie
A1 D. J. Craik
A1 D. J. Adams
YR 2007
UL http://molpharm.aspetjournals.org/content/72/6/1406.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics