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Abstract
Muscarinic toxin 3 (MT3) (65 amino acids, four disulphides, M r 7379) was isolated from the venom of the African snake Dendroaspis angusticeps (green mamba) and its amino acid sequence determined. Its ability to inhibit the binding of [ 3H] N-methylscopolamine ([ 3H]NMS) to Chinese hamster ovary cells stably expressing subtypes of muscarinic receptors was studied. MT3 displayed high affinity for the m4 receptor (p K i = 8.7 ± 0.06), 40-fold lower affinity at m1 receptors (p K i = 7.11 ± 0.17) whereas no inhibition of [ 3H]NMS binding to m2, m3 and m5 receptors was observed at concentrations up to 1 μM. This makes MT3 the most selective m4 receptor ligand known to date.
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