Structure-function relationships among neurotoxic phospholipases: NN-XIII-PLA 2 from Indian cobra (Naja naja naja) and VRV PL-V from Russell's viper (Vipera russelli) venoms

Abstract

Though venom phospholipases induce various pharmacological effects their mechanism of action is in some cases unclear. There may be separate pharmacological sites on the venom phospholipase molecule. In order to understand the structure-function relationships among venom phospholipases, studies on interaction of venom phospholipases with its antibodies and various alkaloids were carried out. The alkaloids aristolochic acid, ajmaline and reserpine were incapable of inhibiting the phospholipase A 2 activity of NN-XIII-PLA 2 but inhibited its edema inducing potency and partially inhibited the symptoms of neurotoxicity. The direct and indirect hemolytic activity remain unaffected. Polyclonal antibodies (anti PL-V Ig) to a neurotoxic PLA 2 VRV PL-V neutralized the neurotoxic symptoms and lethality of VRV PL-V without affecting its in vitro phospholipase A 2 activity when egg PC was used as the substrate. However, they inhibited the catalytic activity of VRV PL-V when synaptosomes were used as the substrate. Our results indicate the presence of multiple pharmacologically active sites apart from catalytic site.