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

FEBS Letters

Lazdunski, Michel¹  Moinier, Danielle¹  Diochot, Sylvie¹  Pacaud, Pierre²  Schweitz, Hugues¹ 

[1] Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UPR 411, 660, route des Lucioles, Sophia Antipolis, 06560 Valbonne, France;Faculté des Sciences et Techniques, Laboratoire de Physiologie Cellulaire, 2 rue de la Houssinière, CRI INSERM 95-08, 44072 Nantes, France

关键词: Venom toxin;    Intestinal muscle;    Ion channel;    Contraction;    MIT1;    mamba intestinal toxin;    BSA;    bovine serum albumin;    TTX;    tetrodotoxin;    L-NAME;    L-N G-nitroarginine methyl ester;    NO;    nitric oxide;   

DOI  :  10.1016/S0014-5793(99)01459-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Mamba intestinal toxin (MIT₁) isolated from Dendroaspis polylepis venom is a 81 amino acid polypeptide cross-linked 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 μM) 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 μM). ¹²⁵I-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.

【 授权许可】

Unknown