Purification and pharmacological characterization of peptide toxins from the black mamba (Dendroaspis polylepis) venom

This paper reports the purification of 28 different Peptides from the venom of the snake Dendroaspis polylepis. These Peptides represent 99% of the total peptide fraction in the venom. The 14 most cationic Peptides form a structurally and functionally homogeneous group of analogs of the most abundant dendrotoxin toxin I (DTXI). They recognize Antibodies raised against DTXI as well as brain membrane binding sites corresponding to K+ channels that are sensitive to DTXI and the bee venom peptide MCD. Similarly to DTXI these 14 Peptides induce convulsions after intracerebroventricular injections in mice and induce GABA release from synaptosomes. However, members in this iso-DTXI family differ widely in their affinity for the DTXI/MCD receptors and in their contractility promoting action on intestinal smooth muscle. The 14 other less cationic Peptides do not interact with the DTXI receptor or with DTXI Antibodies and they do not evoke GABA release. Their targets seem to be essentially of a peripheral nature. Half of them contract guinea pig ileum. In this group of toxins there might be new tools to study membrane excitability.