Structure-function relationships among neurotoxic phospholipases: NN-XIII-PLA2 from Indian cobra (Naja naja naja) and VRV PL-V from Russell's viper (Vipera russelli) venoms.
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 A2 activity of NN-XIII-PLA2 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 PLA2 VRV PL-V neutralized the neurotoxic symptoms and lethality of VRV PL-V without affecting its in vitro phospholipase A2 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.
Bhat
M K
MK
Department of Studies in Biochemistry, University of Mysore, India.
Kasturi
S
S
Gowda
T V
TV
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D002850:Chromatography, Gel; D004487:Edema / Q000139:chemically induced; D004546:Elapid Venoms / Q000737:chemistry*; D008297:Male; D051379:Mice; D010740:Phospholipases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology / Q000633:toxicity*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology / Q000633:toxicity; D054467:Phospholipases A2; D051381:Rats; D012911:Snakes; D013329:Structure-Activity Relationship; D014757:Viper Venoms / Q000737:chemistry*
D000470:Alkaloids; D004546:Elapid Venoms; D014757:Viper Venoms; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2