Title: A snake toxin against muscarinic acetylcholine receptors: amino acid sequence, subtype specificity and effect on guinea-pig ileum Jolkkonen M, Adem A, Hellman U, Wernstedt C, Karlsson E Ref: Toxicon, 33:399, 1995 : PubMed
The sequence of muscarinic toxin 1 (MT1) from Dendroaspis angusticeps (green mamba) was determined (66 amino acids, M(r) 7509). The central part, peptide 25-40, is rich in hydrophobic amino acids, which is a characteristic of muscarinic toxins. MT1 started to inhibit [3H]-NMS (N-methylscopolamine) binding to synaptosomal membranes of porcine brain (contains all five receptor subtypes) at about 1 nM and to membranes from pig heart muscle (only subtype m2) at about 1 microM. Binding of [3H]-AF-DX 384 to heart was inhibited with an IC50 of 14 microM and to brain in two steps. In the first step (IC50 = 32 nM) binding decreased by 37%, indicating that the toxin acted on m1 or m4 receptors, each accounting for about 40% of total receptor content. The second step was similar to the effect on heart. Pirenzepine inhibited binding of [125I]-MT1 to brain receptors with an IC50 of 6.5 nM, corresponding to a Ki of about 6 nM. Literature values of Ki for pirenzepine are 16-18 nM for m1 and > or = 120 mM for other subtypes. This indicates binding to m1 receptors. mM for other subtypes. This indicates binding to m1 receptors. [125I]-MT1 bound to brain with a Kd of 20 nM and a Hill coefficient of 1.0, i.e. one toxin molecule per receptor. In guinea-pig ileum, MT1 (670 nM) produced a rapid contraction, reversible by atropine. The toxin may be an agonist, but might also cause contraction by inducing acetylcholine release by a different mechanism.
        
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Jolkkonen M, Adem A, Hellman U, Wernstedt C, Karlsson E (1995) A snake toxin against muscarinic acetylcholine receptors: amino acid sequence, subtype specificity and effect on guinea-pig ileum Toxicon33: 399-410
Jolkkonen M, Adem A, Hellman U, Wernstedt C, Karlsson E (1995) Toxicon33: 399-410