Cardiotoxin from cobra venom increases the level of phosphatidylinositol 4-monophosphate and phosphatidylinositol kinase activity in two cell lines.
In rat basophilic leukemia-2H3 (RBL-2H3) and Madin-Darby canine kidney (MDCK) cells, cardiotoxin from cobra venom induced a marked decrease in the level of [3H] phosphatidylinositol and a corresponding increase in the level of [3H]phosphatidylinositol 4-monophosphate over the course of 20 min as demonstrated in cells that had been labeled to equilibrium with [3H]inositol. The effect was dependent on the concentration (5-30 micrograms/ml) of the toxin. In plasma membrane-enriched fractions isolated from the two cell lines, the cardiotoxin enhanced the endogenous activity of phosphatidylinositol kinase especially at temperatures above 14 degrees C. In RBL-2H3 cells, cardiotoxin also induced release of substantial amounts of histamine and lactate dehydrogenase. The release of histamine, but not of lactate dehydrogenase, was totally dependent on external calcium and this release probably represented an exocytotic response of the cells to cardiotoxin. Although, initially, treatment with the toxin did not impair antigen-induced hydrolysis of inositol phospholipids or prevent the antigen-induced rise in the concentration of cytosol Ca2+, prolonged exposure to the toxin did result in a progressive loss of responsiveness of RBL-2H3 cells to antigen.
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D001491:Basophils; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D004179:Cobra Cardiotoxin Proteins / Q000494:pharmacology*; D004285:Dogs; D004546:Elapid Venoms / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D007668:Kidney; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
D004179:Cobra Cardiotoxin Proteins; D004546:Elapid Venoms; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C037178:phosphatidylinositol 4-phosphate; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium