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Condylactis toxin: interaction with nerve membrane ionic conductances
Toxlrnn, 1%9, Vol. 7, pp . 247-248. Peryamon Press. Printed In Great Britain
REVIEWS SI~nMana, S. (Shimada Pharmaceutical Institute, No . 4-123, Kohamanaka, Sumiyoshi-ku, Osaka, Japan) . Antifungal steroid glycoside from sea cucumber . Science, N Y. 163, 1462, 1969 . A xaw arrrl>:uxaal, substance, holotoxin, has been isolated from the sea cucumber Stichopus japonicas (Sek.nka). Holotoxin forms colorless needles (m.p. 250° ; decomp .) and shows the following elementary analysis : C 519 per cent, H 793 per cent . It exhibits no absorption in the u.v . The i.r. spectrum which is closely similar to that of holothurin indicates a five-membered ring lactone and one double bond . Holotoxin is supposed to be a steroid glycoside, because after acid hydrolysis theaglycon, which is soluble in chloroform, gives a positive Liebermann-Burchard reaction . Sugars in aqueous solution were detected by a positive reaction to anilino-phosphoric acid reagent and through the reduction of silver oxide. In vitro, holotoxin exhibits high activity against various fungi, including vegetable pathogens, but has scarcely any activity against gram-positive and gram-negative bacteria and mycobacteria . The results of clinical tests with holotoxin against superficial dermatophytosis demonstrated that holotoxin produced some improvement of symptoms in 77 cases out of 87 (885 per cent). Almost no side effects were noted. E.K. War~x>rlt, E. E., SeFll.a~rrelt, Ch. und Scrn~, H. (Organisch chemisches Institut der Univer sititt Zûrich, Switzerland) . Zur Biosynthese des Dendrolasins, eines Inhaltsstoffes der Ameise Zasius fuliginosus Latr. Helv. chienr. Acta 52, l 5, 1969 .
Tx$ s~rxucruxs of dendrolasin (cf. Qunsco et al., Ric. sci. 26,177, 1957 ; Tetrahedron 1, 177, 1957) suggests that this substance is synthesized from isoprenoid units. By feeding the ant Lasius juliginosus Latr. with [l'CJ-1-acetate, [1+cJ-2-acetate, [1KJ]-2-mevalonate, [I'CJ-1-glucose and [l'C]-U-glucose, incorporation ratios of 10 -'-0~15 per cent were obtained in the sesquiterpenoid dendrolasin. It was shown by analysis of the labeling pattern in dendrolasin that the insertions were spread over the whole molecule in exactly the manner that would be expected from terpene biosynthesis . E.K . Tu, A. T. and Toots, P. M. (Dept. of Chemistry, Utah State University, Logan, Utah). Hydro lysis of peptides by snake venoms of Australia and New Guinea. Aust. J. exp. Biol. nred. Sc1. 45, 561, 1967 . P~1^mass substrate specificities of nine venoms of poisonous snakes of Australia and New Guinea were investigated (A . antarcticus, D. superba, N. ater niger, N. ater serventyi, N. scutatus scutatrts, O. scrrtellatus carnri, D. scutellatus scutellatus, P. australis, P. porphyriacus) . Thirty-four peptides (29 dipeptides and 5 tripeptides) were used as substrates. The peptides GIy-L-Asp, GIy-L-Glu, Gly-z-Pro, IrLeu-IrPhe, nt .-Leunl.-Val, rrLys-Gly and 1,-Pro-Gly were not hydrolyzed by any of the venoms . All other dipeptides with the exceptionof rrPhe-l.-Phe were hydrolyzed by all of the venoms investigated. Although the glycylphenylalanine linkage of the tripeptide Gly-t-Phe-r.-Phe was hydrolyzed by each of the venoms investigated, the phenylalanyl-phenylalanine bond was only split by the venoms of N. scutatus scrrtatrts, O. scutellatus scutellatus, and O. scutellatus canai. In like manner, L-Phe-L-Phe was also hydrolyzed only by the venoms of N. scutatrrs scutatus, O. scutellatus cantrt, and O. scutellatus scutellatus. E.K . N~usuxcm_ T., Mocha, J. W. and $HAPIRO, B. I. (Dept. of Physiology and Pharmacology, Duke Univ. Med. Ctr., Durham, N.C . and Biological Labs ., Harvard Univ., Cambridge, Mass.). Condylactis toxin: interaction with nerve membrane ionic conductances. Science, NY. 163, 680,1969.
ConmYl.acrls toxin (cf. $HAPIRO, Toxirnn 5, 233, 1968) from the Bermuda anemone C.'ondylactis gigarttea causes the early transient conductance change of crayfish (Procami5arus clarkil) giant axon membrances to 247
248
Reviews
persist without affecting the shape of its turning-on. The increase in late steady-state conductance is either not affected or slightly suppressed. The effect on the conductance components can adequately account for the prolonged action potential observed in the treated axon. E.K . JAQtrrs, R. (Research Laboratories of the Pharmaceutical Department of Ciba Limited, Basle, Switzerland). The protection afforded by a benzyl glucofuranoside and hydrocortisone against lethal wasp venom shock in the guinea-pig . Pharmacology 2, 21, 1969 . Of gulne8-p1gS with ethyl-3,4,6-tri-O-benzyl glucofuranoside (CIBA 21401-Bu) by oral or parenteral routes protected a proportion of the animals against an otherwise lethal anaphylactoid-like shock produced by the i.v. administration of solutions of crude Vespa vulgaris and Pseudovespa austriaca venoms . Hydrocortisone, parenterally, was a more potent antagonist of the venom, but aspirin and aminopyrine (in doses up to 500 mg per kg orally) were ineffective. A detailed analysis of the protective effect was precluded by shortage of venom. K.R.A . PRS-TREATMENT
MEBS, D. (Isst. f. gerichtl .
u. soziale Med. der Universität, Frankfurt, Germany) . Vergleichende Enzymuntersuchungen an Schlangengiften unter besonderer Berücksichtigung ihrer Caseinspaltenden Proteasen . Hoppe-Seyler's Z. Physlol. Che»~. 349, 1115, 1968 .
enzyme investigations were performed on a series of Elapidae, Viperidae and Crotalidae venoms. Whereas those of Elapidae showed marked esterase activity (5'-nucleotidase, phosphodiesterase, ATP-ase, phospholipase A, cholinesterase), Viperidae and Crotalidac venoms showed marked protease and amino acid esterase (cleavage of casein and HAEE, fibrinogen coagulase, bradykinin-release) activity . The venom of the opisthoglyphous colubrid l.eptodeira onnulata showed caseinolytic activity and low phospholipaseA and phosphodiesterase activity . By ionexchange chromatography and gel filtration two professes were isolated from the venom of Crotalus atrox, one from each of the venoms of Ophiophagus haunah and Leptodelra annulata. All these professes were completely inhibited by EDTA, CN - and Hg, and some activated by Ca'+ and Mgr ions . All split bradykinin at the glycyl-phenyl-alanyl linkageand were not inhibited by soy bean inhibitor and Trasylol . (Author's abstract) COMPARATIVE
SANCHEZ LABRADOR Peces y Aves del Pargeguoy Natural (1767) . M. N. LASTEX . Buenos Aires ; S. A., Compatüa General Fabril
Manuscript prepared by Editors, 511 pp, 1968 .
Ttus Boox presents a rare manuscript written by J. SANCHEZ LABRADOR In 1767 . SANCHEZ LABRADOR contributed one of the most important and useful works on the natural sciences of South America during the eighteenth century. In preparing and editing this work, Castex has presented the heretofore unpublished section on `Fishes and Birds', which is perhaps the most important part of the several sections of Labrador's contribution . The text is an excellent example of the compilation of a little known work on the natural history of South America, particularly of the River Plate region . Castex is to be complimented on this fine contribution to our knowledge of the history of thefauna of South America, as described by this early naturalist . The book, in Spanish, is available at #6 .50. F.E .R.
REVIEWS SI~nMana, S. (Shimada Pharmaceutical Institute, No . 4-123, Kohamanaka, Sumiyoshi-ku, Osaka, Japan) . Antifungal steroid glycoside from sea cucumber . Science, N Y. 163, 1462, 1969 . A xaw arrrl>:uxaal, substance, holotoxin, has been isolated from the sea cucumber Stichopus japonicas (Sek.nka). Holotoxin forms colorless needles (m.p. 250° ; decomp .) and shows the following elementary analysis : C 519 per cent, H 793 per cent . It exhibits no absorption in the u.v . The i.r. spectrum which is closely similar to that of holothurin indicates a five-membered ring lactone and one double bond . Holotoxin is supposed to be a steroid glycoside, because after acid hydrolysis theaglycon, which is soluble in chloroform, gives a positive Liebermann-Burchard reaction . Sugars in aqueous solution were detected by a positive reaction to anilino-phosphoric acid reagent and through the reduction of silver oxide. In vitro, holotoxin exhibits high activity against various fungi, including vegetable pathogens, but has scarcely any activity against gram-positive and gram-negative bacteria and mycobacteria . The results of clinical tests with holotoxin against superficial dermatophytosis demonstrated that holotoxin produced some improvement of symptoms in 77 cases out of 87 (885 per cent). Almost no side effects were noted. E.K. War~x>rlt, E. E., SeFll.a~rrelt, Ch. und Scrn~, H. (Organisch chemisches Institut der Univer sititt Zûrich, Switzerland) . Zur Biosynthese des Dendrolasins, eines Inhaltsstoffes der Ameise Zasius fuliginosus Latr. Helv. chienr. Acta 52, l 5, 1969 .
Tx$ s~rxucruxs of dendrolasin (cf. Qunsco et al., Ric. sci. 26,177, 1957 ; Tetrahedron 1, 177, 1957) suggests that this substance is synthesized from isoprenoid units. By feeding the ant Lasius juliginosus Latr. with [l'CJ-1-acetate, [1+cJ-2-acetate, [1KJ]-2-mevalonate, [I'CJ-1-glucose and [l'C]-U-glucose, incorporation ratios of 10 -'-0~15 per cent were obtained in the sesquiterpenoid dendrolasin. It was shown by analysis of the labeling pattern in dendrolasin that the insertions were spread over the whole molecule in exactly the manner that would be expected from terpene biosynthesis . E.K . Tu, A. T. and Toots, P. M. (Dept. of Chemistry, Utah State University, Logan, Utah). Hydro lysis of peptides by snake venoms of Australia and New Guinea. Aust. J. exp. Biol. nred. Sc1. 45, 561, 1967 . P~1^mass substrate specificities of nine venoms of poisonous snakes of Australia and New Guinea were investigated (A . antarcticus, D. superba, N. ater niger, N. ater serventyi, N. scutatus scutatrts, O. scrrtellatus carnri, D. scutellatus scutellatus, P. australis, P. porphyriacus) . Thirty-four peptides (29 dipeptides and 5 tripeptides) were used as substrates. The peptides GIy-L-Asp, GIy-L-Glu, Gly-z-Pro, IrLeu-IrPhe, nt .-Leunl.-Val, rrLys-Gly and 1,-Pro-Gly were not hydrolyzed by any of the venoms . All other dipeptides with the exceptionof rrPhe-l.-Phe were hydrolyzed by all of the venoms investigated. Although the glycylphenylalanine linkage of the tripeptide Gly-t-Phe-r.-Phe was hydrolyzed by each of the venoms investigated, the phenylalanyl-phenylalanine bond was only split by the venoms of N. scutatus scrrtatrts, O. scutellatus scutellatus, and O. scutellatus canai. In like manner, L-Phe-L-Phe was also hydrolyzed only by the venoms of N. scutatrrs scutatus, O. scutellatus cantrt, and O. scutellatus scutellatus. E.K . N~usuxcm_ T., Mocha, J. W. and $HAPIRO, B. I. (Dept. of Physiology and Pharmacology, Duke Univ. Med. Ctr., Durham, N.C . and Biological Labs ., Harvard Univ., Cambridge, Mass.). Condylactis toxin: interaction with nerve membrane ionic conductances. Science, NY. 163, 680,1969.
ConmYl.acrls toxin (cf. $HAPIRO, Toxirnn 5, 233, 1968) from the Bermuda anemone C.'ondylactis gigarttea causes the early transient conductance change of crayfish (Procami5arus clarkil) giant axon membrances to 247
248
Reviews
persist without affecting the shape of its turning-on. The increase in late steady-state conductance is either not affected or slightly suppressed. The effect on the conductance components can adequately account for the prolonged action potential observed in the treated axon. E.K . JAQtrrs, R. (Research Laboratories of the Pharmaceutical Department of Ciba Limited, Basle, Switzerland). The protection afforded by a benzyl glucofuranoside and hydrocortisone against lethal wasp venom shock in the guinea-pig . Pharmacology 2, 21, 1969 . Of gulne8-p1gS with ethyl-3,4,6-tri-O-benzyl glucofuranoside (CIBA 21401-Bu) by oral or parenteral routes protected a proportion of the animals against an otherwise lethal anaphylactoid-like shock produced by the i.v. administration of solutions of crude Vespa vulgaris and Pseudovespa austriaca venoms . Hydrocortisone, parenterally, was a more potent antagonist of the venom, but aspirin and aminopyrine (in doses up to 500 mg per kg orally) were ineffective. A detailed analysis of the protective effect was precluded by shortage of venom. K.R.A . PRS-TREATMENT
MEBS, D. (Isst. f. gerichtl .
u. soziale Med. der Universität, Frankfurt, Germany) . Vergleichende Enzymuntersuchungen an Schlangengiften unter besonderer Berücksichtigung ihrer Caseinspaltenden Proteasen . Hoppe-Seyler's Z. Physlol. Che»~. 349, 1115, 1968 .
enzyme investigations were performed on a series of Elapidae, Viperidae and Crotalidae venoms. Whereas those of Elapidae showed marked esterase activity (5'-nucleotidase, phosphodiesterase, ATP-ase, phospholipase A, cholinesterase), Viperidae and Crotalidac venoms showed marked protease and amino acid esterase (cleavage of casein and HAEE, fibrinogen coagulase, bradykinin-release) activity . The venom of the opisthoglyphous colubrid l.eptodeira onnulata showed caseinolytic activity and low phospholipaseA and phosphodiesterase activity . By ionexchange chromatography and gel filtration two professes were isolated from the venom of Crotalus atrox, one from each of the venoms of Ophiophagus haunah and Leptodelra annulata. All these professes were completely inhibited by EDTA, CN - and Hg, and some activated by Ca'+ and Mgr ions . All split bradykinin at the glycyl-phenyl-alanyl linkageand were not inhibited by soy bean inhibitor and Trasylol . (Author's abstract) COMPARATIVE
SANCHEZ LABRADOR Peces y Aves del Pargeguoy Natural (1767) . M. N. LASTEX . Buenos Aires ; S. A., Compatüa General Fabril
Manuscript prepared by Editors, 511 pp, 1968 .
Ttus Boox presents a rare manuscript written by J. SANCHEZ LABRADOR In 1767 . SANCHEZ LABRADOR contributed one of the most important and useful works on the natural sciences of South America during the eighteenth century. In preparing and editing this work, Castex has presented the heretofore unpublished section on `Fishes and Birds', which is perhaps the most important part of the several sections of Labrador's contribution . The text is an excellent example of the compilation of a little known work on the natural history of South America, particularly of the River Plate region . Castex is to be complimented on this fine contribution to our knowledge of the history of thefauna of South America, as described by this early naturalist . The book, in Spanish, is available at #6 .50. F.E .R.