Two potent central convulsant peptides, a bee venom toxin, the MCD peptide, and a snake venom toxin, dendrotoxin I, known to block K+ channels, have interacting receptor sites

Abstract

Both the bee venom toxin, mast cell degranulating peptide (MCD peptide) and the mamba toxin dendrotoxin I are potent central convulsants. The two specific receptor sites for these two types of polypeptide toxins are in allosteric interaction in brain membranes. Occupation of the dendrotoxin I binding site (KI = 0.4 nM) prevents binding of the 125I-MCD peptide to its own receptor (KI = 0.23 nM). This inhibition is of the non-competitive type. Autoradiography has shown that a high enough dendrotoxin I concentration (30 nM) prevented binding of 125I MCD peptide to all brain structures where specific receptors had been identified. A lower concentration of the mamba toxin led to a nearly selective inhibition of MCD peptide binding to the hippocampal region which is responsible for the convulsant properties of the 2 types of polypeptide toxins.