Conotoxins: Targeted Peptide Ligands from Snail Venoms

Assessment of Biochemical and Histopathological Effects of Crude Venom of Cone Snail <i>Conus flavidus</i> on <i>albino</i> Mice

“…[40]. The mechanism of paralysis following Conus envenomation could be attributed to junction blockade of nicotinic acetylcholine receptors, as well as inhibition of motor endplate depolarization by sodium channel blockade [45].…”

Biomedical Potential of Marine Natural Products

“…The a-conotoxins (so named because of their pharmacological similarity to the snake a-toxins) were shown to act as antagonists of the nAChR at the endplate region of neuromuscular junctions blocking neuromuscular transmission. This binding was reversible and inhibited by preincubation with other nAChR antagonists, such as a-bungarotoxin (Olivera et al, 1990a). Whole-animal studies showed that the a-conotoxins were selective for nACh receptors at neuromuscular junctions; a-conotoxins-GI and -MI had no effect on blood pressure, heart rate, or responses to vagal and preganglionic stimulation at concentrations which induced paralysis (Marshall and Harvey, 1990).…”

“…contain small, pharmacologically active peptides, which are targeted to various ion channels and receptors. Due to the ability of the conotoxins to discriminate between closely related receptor subtypes, they have become valuable tools for research in neuroscience (Olivera et al, 1990a). f.L-Conotoxin GIIIA (also known as geographutoxin II or GTX II), isolated from the piscivorous cone snail Conus geographus, a 22-residue polycyclic peptide bearing three hydroxyprolines and three disulfide bridges (Olivera et al, 1990a, b), was shown to bind, and hence occlude, site 1 of the sodium channel in skeletal muscle.…”

“…Due to the ability of the conotoxins to discriminate between closely related receptor subtypes, they have become valuable tools for research in neuroscience (Olivera et al, 1990a). f.L-Conotoxin GIIIA (also known as geographutoxin II or GTX II), isolated from the piscivorous cone snail Conus geographus, a 22-residue polycyclic peptide bearing three hydroxyprolines and three disulfide bridges (Olivera et al, 1990a, b), was shown to bind, and hence occlude, site 1 of the sodium channel in skeletal muscle. f.L-Conotoxin GIIIA is an important tool for studying skeletal muscular neurotransmission because it has no discernible effect on sodium channels in cardiac, brain, and nervous tissue (Cruz et al, 1989;Hong and Chang, 1989;Strichartz and Castle, 1990).…”

“…w-Conotoxin GVIA (w-CgTx), a 27-amino acid peptide isolated from C. geographus (Yoshikami et al, 1989;Olivera et al, 1990a, b), is a neuron-specific antagonist with high affinity for voltage-sensitive calcium channels (VSCC) which control neurotransmitter release in response to depolarization of nerve termini. w-Conotoxin GVIA interacted with N-and/or L-type channels, depending upon tissue type, and was also instrumental in characterizing these channel subtypes and their distribution in various tissue (Plummer et al, 1989;Karschin and Lipton, 1989;Yoshikami et al, 1989).…”