Conus peptides targeted to specific nicotinic acetylcholine receptor subtypes.
The venoms of predatory cone snails represent a rich combinatorial-like library of evolutionarily selected, neuropharmacologically active peptides. A major fraction of the venom components are conotoxins--small, disulfide-rich peptides that potently and specifically target components of the neuromuscular system, particularly ligand- and voltage-gated ion channels. This review focuses on Conus peptides, which act at nicotinic acetylcholine receptors. These nicotinic antagonist peptides from Conus are broadly divided into two groups: those that act at the neuromuscular junction and those that act at subtypes of neuronal nicotinic acetylcholine receptors. The latter include peptides specific for the alpha 7, alpha 3 beta 2, and alpha 3 beta 4 nicotinic receptor subtypes. The degree of specificity exhibited by these peptides is remarkable, particularly given their relatively small size. As a group the nicotinic acetylcholine receptor-targeted Conus peptides represent an increasingly well-defined set of tools for probing the structure, function, and physiological role of nicotinic acetylcholine receptors.
McIntosh
J M
JM
Department of Biology, University of Utah, Salt Lake City 84112-0840, USA. mcintosh@bioscience.utah.edu
Santos
A D
AD
Olivera
B M
BM
D000818:Animals; D020916:Conotoxins / Q000737:chemistry / Q000378:metabolism*; D008974:Mollusca / Q000737:chemistry*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000145:classification / Q000378:metabolism*; D013329:Structure-Activity Relationship
D020916:Conotoxins; D011978:Receptors, Nicotinic