POSSIBLE MECHANISMS OF ACTION OF COBRA SNAKE-VENOM CARDIOTOXINS AND BEE VENOM MELITTIN

Cobra snake venom cardiotoxins and bee venom melittin share a number o f pharmacological properties in intact tissues including hemolysis, cy tolysis, contractures of muscle, membrane depolarization and activatio n of tissue phospholipase C and, to a far lesser extent, an arachidoni c acid-associated phospholipase A2. The toxins have also been demonstr ated to open the Ca2+ release channel (ryanodine receptor) and alter t he activity of the Ca2+ + Mg2+-ATPase in isolated sarcoplasmic reticul um preparations derived from cardiac or skeletal muscle. However, a re lationship of these actions in isolated organelles to contracture indu ction has not yet been established. The toxins also bind to and, in so me cases, alter the function of a number of other proteins in disrupte d tissues. The most difficult tasks in understanding the mechanism of action of these toxins have been dissociating the primary from seconda ry effects and distinguishing between effects that only occur in disru pted tissues and those that occur in intact tissue. The use of cardiot oxin and melittin fractions contaminated with trace ('undetectable') a mounts of venom-derived phospholipases A, has continued to be common p ractice, despite the problems associated with the synergism between th e toxins and enzymes and the availability of methods to overcome this problem. With adequate precautions taken with regard to methodology an d interpretation of results, the cobra venom cardiotoxins and bee veno m melittin may prove to be useful probes of a number of cell processes , including lipid metabolism and Ca2+ regulation in skeletal and cardi ac muscle.