MIT1, a black mamba toxin with a new and highly potent activity on intestinal contraction

Mamba intestinal toxin (MIT1) isolated from Dendroaspis polylepis venom is a 81 amino acid polypeptide crosslinked by five disulphide bridges. MIT1 has a very potent action on guinea-pig intestinal contractility. MIT1 (1 nM) potently contracts longitudinal ileal muscle and distal colon, and this contraction is equivalent to that of 40 mM K+. Conversely MIT1 relaxes proximal colon again as potently as 40 mM K+, The MIT1-induced effects are antagonised by tetrodotoxin (1 mu M) in proximal and distal colon but not in longitudinal ileum, The MIT1-induced relaxation of the proximal colon is reversibly inhibited by the NO synthase inhibitor L-NAME (200 mu M). I-125-labelled MIT1 binds with a very high affinity to both ileum and brain membranes (K-d = 1.3 pM and 0.9 pM, and B-max = 30 fmol/mg and 26 fmol/mg, respectively). MIT1 is a very highly selective toxin for a receptor present both in the CNS and in the smooth muscle and which might be an as yet unidentified K+ channel. (C) 1999 Federation of European Biochemical Societies.