Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline transporter

Nat Neurosci. 2001 Sep;4(9):902-7. doi: 10.1038/nn0901-902.

Abstract

Cone snails use venom containing a cocktail of peptides ('conopeptides') to capture their prey. Many of these peptides also target mammalian receptors, often with exquisite selectivity. Here we report the discovery of two new classes of conopeptides. One class targets alpha1-adrenoceptors (rho-TIA from the fish-hunting Conus tulipa), and the second class targets the neuronal noradrenaline transporter (chi-MrIA and chi-MrIB from the mollusk-hunting C. marmoreus). rho-TIA and chi-MrIA selectively modulate these important membrane-bound proteins. Both peptides act as reversible non-competitive inhibitors and provide alternative avenues for the identification of inhibitor drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Carrier Proteins / antagonists & inhibitors*
  • Imaging, Three-Dimensional
  • Magnetic Resonance Spectroscopy
  • Male
  • Molecular Sequence Data
  • Mollusk Venoms / chemistry
  • Mollusk Venoms / classification*
  • Mollusk Venoms / genetics
  • Mollusk Venoms / pharmacology*
  • Neurons / metabolism
  • Norepinephrine Plasma Membrane Transport Proteins
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha / drug effects*
  • Symporters*

Substances

  • Carrier Proteins
  • Mollusk Venoms
  • Norepinephrine Plasma Membrane Transport Proteins
  • Receptors, Adrenergic, alpha
  • Slc6a2 protein, rat
  • Symporters

Associated data

  • PDB/1IEN
  • PDB/1IEO