MIT(1), a black mamba toxin with a new and highly potent activity on intestinal contraction.
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 microM) 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 microM). (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.
Schweitz
H
H
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UPR 411, 660, route des Lucioles, Sophia Antipolis, 06560, Valbonne, France.
Pacaud
P
P
Diochot
S
S
Moinier
D
D
Lazdunski
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001923:Brain Chemistry; D003106:Colon / Q000187:drug effects; D003553:Cystine / Q000737:chemistry; D004546:Elapid Venoms / Q000737:chemistry*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009928:Organ Specificity; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D051381:Rats; D013779:Tetrodotoxin / Q000494:pharmacology
D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C402142:mamba intestinal toxin 1; D013779:Tetrodotoxin; D003553:Cystine