Distribution of Viperaammodytes toxic phospholipase a in the cat and its ability to cross the blood-brain barrier

Abstract Several phospholipases A could be isolated from the venom of the European viper, Vipera ammodytes , having different specific activities toward egg lecithin and different lethalities. The most lethal of these enzymes is fraction “k 2 ” having an intravenous LD 50 for white mice of 0.021 mg per kg and a specific activity of 280 μM/min mg at 40 °C. The enzyme could be labeled with 131 I without loosing its enzymatic activity and lethality. The passage of this enzyme from blood into cerebrospinal fluid (CSF) was followed in anesthesized cats. Approximately 1% of the blood level of the enzyme was found in CSF indicating the ability of this protein to penetrate the blood-brain barrier. Although the lethality of fraction “k 2 ” becomes as low as 0.085 μg/kg when applied intraventricularly, it is not very likely that the central effects of this fraction are of major importance in envenomation since the distribution pattern of the labeled enzyme shows that most of the protein remains in liver, lungs and kidneys, presumably non-selectively bound to membranes and only 0.2% of the injected fraction can reach the brain. Relatively high amount of enzyme was also found in the diaphragm. The penetration of the blood-brain barrier of the radiolabeled phospholipase is within the limits for the proteins of this size (M.w. 14 500).