Effects of divalent cations on snake venom cardiotoxin-induced hemolysis and 3H-deoxyglucose-6-phosphate release from human red blood cells.
At a low concentration of Naja naja kaouthia cardiotoxin (3 microM) Ca2+, Sr2+ and Ba2+ (2 mM), had little to no effect on 3H-deoxyglucose-6-phosphate (3H-dGlu-6-p) or hemoglobin release. At higher concentrations of N. n. kaouthia cardiotoxin (greater than or equal to 10 microM), Ca2+ (2 mM), but not Sr2+ or Ba2+, significantly enhanced 3H-dGlu-6-p and hemoglobin release. Mn2+ (2 mM) almost completely inhibited 3H-dGlu-6-p release and hemolysis at both the 3 microM and 10 microM concentrations of cardiotoxin. At a fixed concentration of N. n. kaouthia cardiotoxin (3 microM). Ca2+ at low concentrations (0.5 mM) enhanced 3H-dGlu-6-p and hemoglobin release, but at higher concentrations caused a dose-dependent inhibition of cardiotoxin action. The cardiotoxin from N. n. kaouthia venom (3 microM) induced 3H-dGlu-6-p release and hemolysis release with similar time courses and to similar extents. 3H-dGlu-6-p release induced by cardiotoxin was greatly enhanced as the pH of the medium was increased from 7.0 to 8.5. Similarities between 3H-dGlu-6-p and hemoglobin release do not support opening of pores in the plasmalemma of all red blood cells as the mode of action of cardiotoxins, but suggests that complete lysis of a subpopulation of cells occurs. Cardiotoxins have two components of lysis, only one of which is Ca2+-dependent. The Ca2+-dependent lysis is only evident at higher cardiotoxin concentrations and is likely due to trace phospholipase A2 contamination in the toxin fraction. Mn2+ is an effective antagonist of cardiotoxin action.
Jiang
M S
MS
Department of Anesthesiology, Hahnemann University, Philadelphia, PA 19102-1192.
Fletcher
J E
JE
Smith
L A
LA
D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology*; D004179:Cobra Cardiotoxin Proteins / Q000037:antagonists & inhibitors*; D004546:Elapid Venoms / Q000037:antagonists & inhibitors*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000097:blood*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008345:Manganese / Q000494:pharmacology; D013324:Strontium / Q000494:pharmacology
D002413:Cations, Divalent; D004179:Cobra Cardiotoxin Proteins; D004546:Elapid Venoms; D005958:Glucosephosphates; D001464:Barium; C015785:2-deoxyglucose-6-phosphate; D008345:Manganese; D019298:Glucose-6-Phosphate; D002118:Calcium; D013324:Strontium