title: Oxylepitoxin-1, a reversible neurotoxin from the venom of the inland taipan (Oxyuranus microlepidotus).
abstract: This study describes the characterization of oxylepitoxin-1 (MW 6789), the first postsynaptic neurotoxin isolated from the venom of the Inland taipan (Oxyuranus microlepidotus), which is the most venomous snake in the world. Oxylepitoxin-1, purified using successive steps of size-exclusion and reverse phase-high performance liquid chromatography, produced concentration-dependent (0.3-1.0 microM) inhibition of nerve-mediated (0.1 Hz, 0.2 ms, supramaximal V) twitches of the chick biventer cervicis nerve-muscle preparation. Taipan antivenom (5units/ml) prevented the neurotoxic activity of whole venom (10 microg/ml), but had no significant effect on oxylepitoxin-1 (1 microM). The toxin-induced inhibition of nerve-mediated twitches was significantly reversed upon washing the tissue at 5 min intervals. Oxylepitoxin-1 (30-300 nM) displayed competitive antagonism at the skeletal muscle nicotinic receptor with a pA(2) value of 7.16+/-0.28 (i.e. approximately 10-fold more potent than tubocurarine). The venom had a high level of PLA(2) activity (765+/-73 micromol/min/mg) while oxylepitoxin-1 displayed no PLA(2) activity. Partial N-terminal sequencing of oxylepitoxin-1 shows high sequence identity (i.e. 93%) to postsynaptic toxins isolated from the venom of the closely related coastal taipan (Oxyuranus scutellatus scutellatus).
authors.affiliation: Monash Venom Group, Department of Pharmacology, Monash University, Victoria 3800, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Clarke
authors.forename: Sanjaya
authors.initials: S
authors.lastname: Kuruppu
authors.forename: Shane
authors.initials: S
authors.lastname: Reeve
authors.forename: A
authors.initials: A
authors.lastname: Ian Smith
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Hodgson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000997:Antivenins / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000737:chemistry* / Q000302:isolation & purification; D017815:Elapidae; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000302:isolation & purification*; D016415:Sequence Alignment
chemical_list: D000997:Antivenins; D004546:Elapid Venoms; D009498:Neurotoxins; C519181:oxylepitoxin-1 protein, Oxyuranus microlepidotus; D002217:Carbachol