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MIT 1 , a black mamba toxin with a new and highly potent activity on intestinal contraction
Author(s) -
Schweitz Hugues,
Pacaud Pierre,
Diochot Sylvie,
Moinier Danielle,
Lazdunski Michel
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01459-3
Subject(s) - tetrodotoxin , contraction (grammar) , ileum , contractility , toxin , chemistry , muscle contraction , guinea pig , medicine , endocrinology , biochemistry , biology
Mamba intestinal toxin (MIT 1 ) isolated from Dendroaspis polylepis venom is a 81 amino acid polypeptide cross‐linked by five disulphide bridges. MIT 1 has a very potent action on guinea‐pig intestinal contractility. MIT 1 (1 nM) potently contracts longitudinal ileal muscle and distal colon, and this contraction is equivalent to that of 40 mM K + . Conversely MIT 1 relaxes proximal colon again as potently as 40 mM K + . The MIT 1 ‐induced effects are antagonised by tetrodotoxin (1 μM) in proximal and distal colon but not in longitudinal ileum. The MIT 1 ‐induced relaxation of the proximal colon is reversibly inhibited by the NO synthase inhibitor L‐NAME (200 μM). 125 I‐labelled MIT 1 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). MIT 1 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.