Two new classes of conopeptides inhibit the α1-adrenoceptor and noradrenaline transporter

Authors

Iain A. Sharpe, University of Queensland
John Gehrmann, University of Queensland
Marion L. Loughnan, University of Queensland
Linda Thomas, University of Queensland
Denise Adams, University of Queensland
Ann Atkins, University of Queensland
Elka Palant, University of Queensland
David J. Craik, University of Queensland
David J. Adams, University of QueenslandFollow
Paul F. Alewood, University of Queensland
Richard J. Lewis, University of QueenslandFollow

RIS ID

106090

Publication Details

Sharpe, I. A., Gehrmann, J., Loughnan, M. L., Thomas, L., Adams, D. A., Atkins, A., Palant, E., Craik, D. J., Adams, D. J., Alewood, P. F. & Lewis, R. J. (2001). Two new classes of conopeptides inhibit the α1-adrenoceptor and noradrenaline transporter. Nature Neuroscience, 4 (9), 902-907.

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 α1-adrenoceptors (p-TIA from the fish-hunting Conus tulipa), and the second class targets the neuronal noradrenaline transporter (ξ-MrIA and ξ-MrIB from the mollusk-hunting C. marmoreus), p-TIA and ξ-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.