1. Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline transporter.
- Author
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Sharpe IA, Gehrmann J, Loughnan ML, Thomas L, Adams DA, Atkins A, Palant E, Craik DJ, Adams DJ, Alewood PF, and Lewis RJ
- Subjects
- Amino Acid Sequence genetics, Animals, Imaging, Three-Dimensional, Magnetic Resonance Spectroscopy, Male, Molecular Sequence Data, Mollusk Venoms chemistry, Mollusk Venoms genetics, Neurons metabolism, Norepinephrine Plasma Membrane Transport Proteins, Rats, Rats, Wistar, Carrier Proteins antagonists & inhibitors, Mollusk Venoms classification, Mollusk Venoms pharmacology, Receptors, Adrenergic, alpha drug effects, Symporters
- 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.
- Published
- 2001
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