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 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 (pKi = 8.7 +/- 0.06), 40-fold lower affinity at ml receptors (pKi = 7.11 +/- 0.17) whereas no inhibition of [3H]NMS binding to m2, m3 and m5 receptors was observed at concentrations up to 1 microM. This makes MT3 the most selective m4 receptor ligand known to date.
Jolkkonen
M
M
Department of Biochemistry, Biomedical Centre, Uppsala, Sweden.
van Giersbergen
P L
PL
Hellman
U
U
Wernstedt
C
C
Karlsson
E
E
D000470:Alkaloids / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D004546:Elapid Venoms / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D017815:Elapidae; D005663:Furans; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008969:Molecular Sequence Data; D009281:Naphthalenes; D010455:Peptides / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D010880:Piperidines; D010890:Pirenzepine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*; D017421:Sequence Analysis
D000470:Alkaloids; D000596:Amino Acids; D004546:Elapid Venoms; D005663:Furans; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes; D010455:Peptides; D010880:Piperidines; D011976:Receptors, Muscarinic; C089528:muscarinic toxin 3; D010890:Pirenzepine; C048172:himbacine