Mode of Action of Membrane Perturbing Agents: Snake Venom Cardiotoxins and Phospholipases A
Abstract
Cardiotoxins (CTXs) are potent membrane perturbing agents that interact in mutual synergism with phospholipase A2 (PLA2). The CTXs selectively lyse a subpopulation of older red blood cells (RBCs), as determined by similarities between hemoglobin and 3H-deoxyglucose-6-p release. This lysis is enhanced by low concentrations of CA2+, through activation of PLA2 activity, and inhibited by high concentrations of Ca2+. Hemolysis is antagonized completely by Mn2+ and competitively by low concentrations of sphingosine and polymyxin B. Other protein kinase C and calmodulin inhibitors are ineffective antagonists of CTX action. A PLA2 with CTX-like properties irreversibly alters the response of CA2+ -regulated voltage-dependent K+ channels by locking on A Ca2+ -dependent process, despite only a slight transient increase in intracellular CA2+ levels. Melittin, a model for CTX action, can remove barriers blocking the membrane penetrating capability of PLA2. Melittin and CTX fractions contaminated with even trace PLA2 activity have dramatic effects on fatty acid release that could wrongfully by interpreted as activation of an endogenous (tissue) PLA2. Effects of both of these agents on tissue lipase activity will be examined in year three. Keywords: RA 1, Membrane active compounds; Phospholipase A; Snake venom cardiotoxins; Toxins; Snake venoms; Membrane biology.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 15, 1989
- Accession Number
- ADA213538
Entities
People
- Jeffrey E. Fletcher