Dendrotoxin from the venom of the green mamba, Dendroaspis angusticeps
The venom of the green mamba, Dendroaspis angusticeps has previously been shown to produce neuromuscular facilitation by increasing acetylcholine release. After gel filtration and ion-exchange chromatography of the whole venom, a basic polypeptide with facilitatory actions was isolated. This polypeptide, named dendrotoxin, has 59 amino acid residues, probably with only 3 disulphide bonds and a blocked N-terminus.
When injected into conscious mice, dendrotoxin made the mice hypersensitive to external stimuli and subsequently produced respiratory paralysis. When tested on the isolated chick biventer cervicis nerve-muscle preparation, concentrations of dendrotoxin of 0.5 μg/ml (7×10−8 M) and greater, increased responses to indirect stimulation by 200–250%, without any increase in responses to submaximal concentrations of exogeneous acetylcholine, carbachol, KCl or direct stimulation. The augmentation was slow to develop, not reversed by washing, and could last several hours before slowly waning. Dendrotoxin did not produce spontaneous twitching or contractures.
It is concluded that dendrotoxin is not an anticholinesterase, does not affect receptor sensitivity or muscle contractility, but produces twitch augmentation by increasing the amount of acetylcholine released by nerve stimulation. Thus, dendrotoxin appears to represent a snake venom neurotoxin with unusual chemical and pharmacological properties.
Key wordsSnake venoms Dendroaspis angusticeps Neurotoxins Neuromuscular facilitation Acetylcholine release
Unable to display preview. Download preview PDF.
- Ambler, R. P.: Carboxypeptidases A and B. Methods in enzymology XI, 436–445 (1967)Google Scholar
- Barrett, J. C., Harvey, A. L.: Effects of the venom of the green mamba, Dendroaspis angusticeps on skeletal muscle and neuromuscular transmission. Br. J. Pharmacol. 67, 199–205 (1979)Google Scholar
- Bock, R. M., Ling, N. S.: Devices for gradient elution in chromatography. Anal. Chem. 26, 1543–1546 (1954)Google Scholar
- Bowman, W. C., Harvey, A. L., Marshall, I. G.: The actions of aminopyridines on avian muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 99–103 (1977)Google Scholar
- Ginsborg, B. L., Warriner, J.: The isolated chick biventer cervicis nerve-muscle preparation. Br. J. Pharmacol. 15, 410–411 (1960)Google Scholar
- Halpert, J., Eaker, D.: Amino acid sequence of a neurotoxic phospholipase A from the venom of the Australian tiger snake Notechis scutatus scutatus. J. Biol. Chem. 250, 6990–6997 (1975)Google Scholar
- Harvey, A. L., Marshall, I. G.: The facilitatory actions of aminopyridines and tetraethylammonium on neuromuscular transmission and muscle contractility in avian muscle. Naunyn-Schmiedeberg's Arch. Pharmacol. 299, 53–60 (1977a)Google Scholar
- Harvey, A. L., Marshall, I. G.: The actions of three diaminopyridines on the chick biventer cervicis muscle. Eur. J. Pharmacol. 44, 303–309 (1977b)Google Scholar
- Joubert, F. J., Strydom, D. J.: Snake venoms. The amino-acid sequence of trypsin inhibitor E of Dendroaspis polylepis polylepis (Black mamba) venom. Eur. J. Biochem. 87, 191–198 (1978)Google Scholar
- Karlsson, E., Arnberg, H., Eaker, D.: Isolation of the principal neurotoxins of two Naja naja subspecies. Eur. J. Biochem. 21, 1–16 (1971)Google Scholar
- Karlsson, E., Eaker, D., Fryklund, L., Kadin, S.: Chromatographic separation of Enhydrina schistosa (common sea snake) venom and the characterization of two principal neurotoxins. Biochemistry 11, 4628–4633 (1972)Google Scholar
- Sober, H. A.: Handbook of Biochemistry, 2nd edition, pp. B74–75. Cleveland: The Chemical Rubber Co. 1970Google Scholar
- Strydom, D. J.: Protease inhibitors as snake venom toxins. Nat. New Biol. 243, 88–89 (1973)Google Scholar
- Tamiya, N., Arai, H.: Studies on sea snake venoms: crystallization of erabutoxins a and b from Laticauda semifasciata venom. Biochem. J. 99, 624–630 (1966)Google Scholar