Accession Number : ADA201836

Title :   Mode of Action of Membrane Perturbing Agents: Snake Venom Cardiotoxins and Phospholipases A.

Descriptive Note : Annual rept. 15 Jun 87-14 Jun 88,

Corporate Author : HAHNEMANN UNIV SCHOOL OF MEDICINE PHILADELPHIA PA

Personal Author(s) : Fletcher, Jeffrey E.

Report Date : 01 JUL 1988

Pagination or Media Count : 44

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)

Descriptors :   *ERYTHROCYTES, *MUSCULOSKELETAL SYSTEM, *PHOSPHOLIPIDS, *SNAKES, *VENOMS, ADDITION, CHANNELS, CONTAMINATION, ELEVATION, FATTY ACIDS, LOW LEVEL, MEMBRANES, MUSCLES, PERMEABILITY, PERTURBATIONS, POTENCY, PRODUCTION, RELEASE, SENSITIVITY, SIGNALS, TRANSDUCERS, TRANSIENTS.

Subject Categories : Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE