A TOXIN FROM THE GREEN MAMBA DENDROASPIS-ANGUSTICEPS - AMINO-ACID-SEQUENCE AND SELECTIVITY FOR MUSCARINIC M4 RECEPTORS

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