Purification and sequence of a presynaptic peptide toxin from Conus geographus venom

Abstract

A novel toxin, omega-conotoxin (omega-CgTX), from the venom of the fish-eating marine mollusc Conus geographus has been purified and biochemically characterized. Recently, this omega-conotoxin has been shown to inhibit the voltage-activated entry of Ca2+, thus providing a potentially powerful probe for exploring the vertebrate presynaptic terminal [Kerr, L. M., & Yoshikami, D. (1984) Nature (London) 308, 282-284]. The toxin is a basic 27 amino acid peptide amide with three disulfide bridges. An unusual feature is a remarkable preponderance of hydroxylated amino acids. The sequence of omega-CgTx GVIA is Cys-Lys-Ser- Hyp-Gly5-Ser-Ser-Cys-Ser-Hyp10-Thr-Ser-Tyr-Asn-Cys15-C ys-Arg-Ser- Cys-Asn20-Hyp-Tyr-Thr-Lys-Arg25-Cys-Tyr-NH2.

Evidence for a dihydropyridine‐sensitive and conotoxin‐insensitive release of noradrenaline and uptake of calcium in adrenal chromaffin cells

“…The peptide co-conotoxin has been shown in certain preparations to attenuate depolarizationevoked release of neurotransmitter (Olivera et al, 1984;Kerr & Yoshikama, 1984;Reynolds et al, 1986;Rivier et al, 1987;Sano et al, 1987;Dooley et al, 1987;Mohy El-Din & Malik, 1988;Maggi et al, 1988;Herdon & Nahorski, 1988). On the basis of electrophysiological evidence it has been suggested that this toxin blocks both L and N type neuronal VSCC (McCleskey et al, 1987;Cruz et al, 1987), consistent with the suggestion that release is mediated principally by these two channel types (Miller, 1987).…”

Molecular cloning of a murine N‐type calcium channel α1 subunit

“…At least six different genes have been identified [24], and an even greater functional variety might be produced by alternate splicing of the different gene products. The N-type Ca2' channel which is inhibited by w-Conotoxin GVIA (wCgTx) plays an important role in neuronal tissues [5,6]. For example wCgTx inhibits the secretion of neurotransmitters stimulated by depolarisation [7,8].…”

Effect of an intracellular calcium chelator on the regulation of electrically evoked [3H]‐noradrenaline release from rat hippocampal slices

“…We have also examined how such treatment alters the regulation of neurotransmitter release by adenosine Al-receptor agonists and a2-adrenoceptor agonists. Finally, we have compared the effect of these presynaptic agonists with the effect of a compound, w-conotoxin, that is known to interact specifically with calcium entry, mainly through N-type Ca2+-channels (Olivera et al, 1984;Reynolds et al, 1986;Miller, 1988).…”