Poster Presentation 2014 International Biophysics Congress

A new target for the alpha-conotoxins: The GABA(B) receptor (#288)

Richard J. Clark 1 , Bodil B. Carstens 2 , Geza Berecki 3 , Brid C. Callaghan 3 , David J. Craik 2 , David J. Adams 3
  1. School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia
  2. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
  3. Innovations Research Institute, RMIT University, Melbourne, Victoria, Australia

Conotoxins are peptide toxins, ranging in size from 12 to 30 amino acids, isolated from the venom of snails from the Conus genus [1]. Members of this peptide family target a range of membrane receptors with both high potency and selectivity and as a consequence are useful as neurological probes and have a range of potential pharmaceutical applications. A subfamily of conotoxins, the alpha-conotoxins, were believed to interact only with nicotinic acetylcholine receptors (nAChRs), which have been implicated in a range of disorders, including Alzheimers disease, schizophrenia, depression and small cell lung carcinoma and also play a role in analgesia and addiction [2]. However, recently we showed that a subset of the alpha-conotoxins also modulate N-type calcium channels by acting as agonists of the G-protein-coupled GABAB receptor [3]. GABAB receptors [4] are G-protein coupled receptors for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter of the brain, and are a promising target for the treatment of a range of neurological and psychiatric disorders including pain, depression and drug addiction [5]. One member of this conotoxin subset, Vc1.1, has now been developed as an orally active lead molecule for the treatment of neuropathic pain [6]. This presentation will describe our discovery that certain alpha-conotoxins target the GABAB receptor, our efforts towards defining the molecular details of this interaction.

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