A toxin from the green mamba Dendroaspis angusticeps: Amino acid sequence and selectivity for muscarinic m4 receptors

• Published in: FEBS letters 1994-09, Vol.352 (1), p.91-94
• Main Authors: Jolkkonen, Mikael, van Giersbergen, Paul L.M., Hellman, Ulf, Wernstedt, Christer, Karlsson, Evert
• Format: Article
• Language: English
• Subjects: Alkaloids - metabolism; Amino Acid Sequence; Amino Acids - analysis; Animals; Dendroaspis angusticeps; Dendroaspis angusticeps toxin; Elapid Venoms - chemistry; Elapid Venoms - isolation & purification; Elapid Venoms - metabolism; Elapidae; Furans; Kinetics; Molecular Sequence Data; Muscarinic m4 receptor; Naphthalenes; Peptides - genetics; Peptides - isolation & purification; Peptides - metabolism; Piperidines; Pirenzepine - metabolism; Receptors, Muscarinic - metabolism; Sequence Analysis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(94)00933-3

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.