Summary
Lyophilized venom of Naja naja atra was fractionated on column of CM-Sephadex C-50 into 12 fractions by gradient elution with ammonium acetate buffer at pH 5–7. Among them 5 fractions (V–IX) were found to be neurotoxic and 3 (X–XII) to be cardiotoxic. Intraperitoneal LD50 in mice was 0.074 µg/g for the major neurotoxic component (Fr. VIII) and 1.48 µg/g for the major cardiotoxic one (Fr. XII). The latter, named cardiotoxin, caused contracture followed by paralysis of the chick biventer cervicis muscle, the frog sartorius muscle and the rat diaphragm, in consequence of irreversible depolarization of the cell membrane. In the absence of calcium no contracture was produced, although the depolarizing effect remained unchanged. Cardiotoxin caused systolic arrest of the isolated frog heart and the rat atrium, probably by the same mechanism. It also caused a contraction of the guinea-pig ileum, which was largely antagonized by atropine but not by hexamethonium or pyribenzamine. In the presence of cardiotoxin the responses of the ileum to nicotine and to submaximal transmural stimulation were first enhanced and then depressed. Cardiotoxin caused vasoconstriction of the rabbit ear vessels, which was largely antagonized by phenoxybenzamine. It also produced local irritation of the rabbit conjunctiva and the rat hind paw. In cats, cardiotoxin caused a fall in the systolic pressure much more than the diastolic pressure, accompanied by various ECG changes, such as P–R interval prolongation, decreased amplitude of QRS, S–T and T changes, ventricular premature beats, complete A–V block, idioventricular rhythm etc. It is concluded that cardiotoxin acts on various kinds of cells in the animal body, causing irreversible depolarization of the cell membrane and consequently impairing its functions.
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References
Boquet, P.: Constitution chimique des venins de serpents et immunite antivenimeuse. Toxicon 3, 243–279 (1966).
Bülbring, E.: Observations on the isolated phrenic nerve diaphragm preparation of the rat. Brit. J. Pharmacol. 1, 38–61 (1946).
Burn, J. H.: Practical Pharmacology, 22–25. Oxford: Blackwell Sci. Pub. 1952.
Chang, C. C., and C. Y. Lee: Electrophysiological study of neuromuscular blocking action of cobra neurotoxin. Brit. J. Pharmacol. 28, 172–182 (1966).
Fatt, P., and B. Katz: An analysis of the end-plate potential recorded with an intra-cellular electrode. J. Physiol. (Lond.) 115, 320–370 (1951).
Ginsborg, B. L., and J. Warriner: The isolated chick biventer cervicis nervemuscle preparation. Brit. J. Pharmacol. 15, 410–411 (1960).
Kellaway, C. H., R. O. Cherry, and F. E. Williams: The peripheral action of the Australian snake venoms. II. The curari-like action in mammals. Aust. J. exp. Biol. med. Sci. 10, 181–194 (1932).
Lee, C. Y., C. C. Chang, T. H. Chiu, T. C. Tseng, and S. Y. Lee: Pharmacological properties of cardiotoxin isolated from the venom of Naja naja atra. Proc. Int. Symp. Animal Venoms, São Paulo (Brasil) 1966.
——, and M. T. Peng: An analysis of the respiratory failure produced by the Formosan elapid venoms. Arch. int. Pharmacodyn. Ther. 133, 180–192 (1961).
-- L. F. Tseng, and T. H. Chiu: Absorption and distribution of cobra (Naja naja atra) venom and its purified toxins (neurotoxin and cardiotoxin) following envenomation. VII Int. Congress Biochem., Tokyo 1967.
Litchfield, J. T., and F. Wilcoxon: A simplified method of evaluating dose-effect experiments. J. Pharmacol. exp. Ther. 96, 99–113 (1949).
Lo, T. B., and Q. L. Chang: Chemical studies of Formosan cobra (Naja naja atra) venom. Part III. N-terminal amino acid analysis of some purified protein components by DNP and DNS methods. J. Chinese Chem. Soc., Ser. II, 13, 203–209 (1966).
—— and C. Y. Lee: Chemical studies of Formosan cobra (Naja naja atra) venom. Part I. Chromatographic separation of crude venom on CM-Sephadex and preliminary characterization of its components. J. Chinese Chem. Soc., Ser. II, 13, 25–37 (1966).
Meldrum, B. S.: The actions of snake venom on nerve and muscle. The pharmacology of phospholipase A and of polypeptide toxins. Pharmac. Rev. 17, 393–445 (1965).
Raudonat, H. W., and R. Holler: Über die herzwirksame Komponente des Kobragiftes (Cardiotoxin). Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 233, 431–437 (1958).
Sarkar, N. K.: Isolation of cardiotoxin from cobra venom (Naja tripudians, monocellate variety). J. Indian chem. Soc. 24, 227–232 (1947a).
—— Determination of molecular weight of Cardiotoxin by diffusion method. J. Indian chem. Soc. 24, 61–64 (1947b).
—— Action mechanism of cobra venom, cardiotoxin and allied substances on muscle contraction. Proc. Soc. exp. Biol. (N. Y.) 78, 469–471 (1951).
Slotta, K. H.: Chemistry and biochemistry of snake venoms. Fortschr. Chem. org. Naturst. 12, 406–465 (1955).
Su, C., C. C. Chang, and C. Y. Lee: Pharmacological properties of the neurotoxin of cobra venom. Animal Toxins, pp. 259–267. Oxford and New York: Pergamon press 1967.
Tseng, T. C.: A study on cardiotoxin isolated from Formosan cobra venom. M. S. Thesis. National Taiwan University 1964.
Vick, J. A., H. P. Ciuchta, and E. H. Polley: The effect of cobra venom on the respiratory mechanism of the dog. Arch. int. Pharmacodyn. 153, 424–429 (1965).
Yang, C. C.: Crystallization and properties of cobrotoxin from Formosan cobra venom. J. biol. Chem. 240, 1616–1618 (1965).
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Supported by the U.S. Army Med. Res. Develop. Command Res. Grant DA-MD-49-193-66-G182 and by the National Council on Science Development, Republic of China.
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Lee, C.Y., Chang, C.C., Chiu, T.H. et al. Pharmacological properties of cardiotoxin isolated from Formosan cobra venom. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 259, 360–374 (1968). https://doi.org/10.1007/BF00536909
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DOI: https://doi.org/10.1007/BF00536909