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          Document History for Document ID 292180

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Document Version Version Comment Date Status
292180.0 [No comment] 13.12.2006 11:01 Released

ID: 292180.0, MPI für experimentelle Medizin / MCN
Synthetic μO-conotoxin MrVIB blocks TTX-resistant sodium channel Na(V)1.8 and has a long-lasting analgesic activity
Authors:Bulaj, Gregorz; Zhang, Min-Min; Green, Brad R.; Fiedler, Brian; Layer, Richard T.; Wei, Sue; Nielsen, Jacob S.; Low, Scott J.; Klein, Brian D.; Wagstaff, John D.; Chicoine, Linda; Harty, T. Patrick; Terlau, Heinrich; Yoshikami, Doju; Olivera, Baldomero M.
Language:English
Date of Publication (YYYY-MM-DD):2006-06
Title of Journal:Biochemistry
Journal Abbrev.:Biochemistry
Volume:45
Issue / Number:23
Start Page:7404
End Page:7414
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:mu O-Conotoxin MrVIB is a blocker of voltage-gated sodium channels, including TTX-sensitive and -resistant subtypes. A comprehensive characterization of this peptide has been hampered by the lack of sufficient synthetic material. Here, we describe the successful chemical synthesis and oxidative folding of MrVIB that has made an investigation of the pharmacological properties and therapeutic potential of the peptide feasible. We show for the first time that synthetic MrVIB blocks rat Na(V)1.8 sodium channels and has potent and long-lasting local anesthetic effects when tested in two pain assays in rats. Furthermore, MrVIB can block propagation of action potentials in A- and C-fibers in sciatic nerve as well as skeletal muscle in isolated preparations from rat. Our work provides the first example of analgesia produced by a conotoxin that blocks sodium channels. The emerging diversity of antinociceptive mechanisms targeted by different classes of conotoxins is discussed.
Free Keywords:NEURONAL NA+ CHANNELS; ROOT GANGLION NEURONS; DELTA-CONOTOXIN; NEUROPATHIC PAIN; SENSORY NEURONS; CONUS-MARMOREUS; RECEPTOR-SITE; VENOM; CURRENTS; PEPTIDE
External Publication Status:published
Document Type:Article
Communicated by:Heinrich Terlau
Affiliations:MPI für experimentelle Medizin/MCN
External Affiliations:Dept. of Biology, University of Salt Lake City, Utah 84112; Cognetix Inc., 421 Wakara Way, Salt Lake City, Utah 84108
Identifiers:ISSN:0006-2960 [ID No:1]
ISI:000238047600040 [ID No:2]
ISI:000238047600040 [ID No:3]
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