Mode of Action of Membrane Perturbing Agents: Snake Venom Cardiotoxins and Phospholipases A.
Abstract
CTXs are potent membrane perturbing agents that interact with phospholipase a2 (PLA2). The mode of action of snake venom CTXs in skeletal muscle seems similar to that in red blood cells. The CTXs do not cause a gross alteration in membrane permeability, but instead specifically alter membrane channels and cause transient elevations in free cytoplasmic Ca2+levels. How these events are related remains to be determined. It is not clear at this time what accounts for the differences in the sensitivity of erythrocytes and muscle to trace contamination of the CTX preparation with PLA2. Oddly, red blood cells with low levels of free fatty acid are more sensitive to CTX action. Yet exogenous addition of free fatty acids, or production of free fatty acids from red blood cell phospholipids treated with exogenously added PLA2 greatly increases the potency of CTXs. The CTXs themselves appear to exhibit fatty acid releasing activity that is most likely a combination of PLA1 and PLA2 activities. The CTXs most likely cause their effects through signal transduction, not internalization. Considerable work remains to understand the basic mechanism of action of CTX and the role of free fatty acids in that mechanism. (mjm)
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1988
- Accession Number
- ADA201836
Entities
People
- Jeffrey E. Fletcher