SOME PHARMACOLOGICAL STUDIES OF VENOM FROM THE INLAND TAIPAN (OXYURANUS-MICROLEPIDOTUS)

The present study was designed to obtain a basic pharmacological profi le of venom from the inland taipan (Oxyuranus microlepidotus). Venom ( 0.05-50 mu g/ml) produced dose-dependent contractions in guinea-pig il eum, which could not be reproduced upon second administration. The cyc looxygenase inhibitor indomethacin (1 mu M), a preceding anaphylactic response induced by egg albumin and inactivation of phospholipase A(2) (PLA(2)) by incubation with 4-bromophenacyl bromide (1.8 mM) all sign ificantly inhibited responses to venom (0.5 mu g/ml). Venom (0.5 mu g/ ml) caused inhibition of stimulation-induced contractions in the prost atic segment of rat vas deferens which was not significantly affected by the alpha(2)-adrenoceptor antagonist idazoxan (0.3 mu M). Venom (10 mu g/ml) caused time-dependent inhibition of the rat electrically sti mulated phrenic nerve-diaphragm preparation, positive inotropic and ch ronotropic responses in rat isolated atria and relaxation in rat endot helium-denuded and -intact isolated aortae. In endothelium-intact aort ae, the nitric oxide synthase inhibitor N-nitro-L-arginine (NOLA, 0.1 mM) significantly inhibited the response to venom (10 mu g/ml). Venom (50 mu g/kg, i.v.) caused an immediate drop in blood pressure followed by cardiovascular collapse in anaesthetised rats. Venom (10 mu g/kg, i.v.) caused a gradual fall in blood pressure which was sometimes acco mpanied by a temporary cessation of respiration. A PLA(2) assay detect ed the presence of PLA(2) in the venom. These results suggest that the venom contains a component capable of causing the synthesis of arachi donic acid metabolites and a component capable of relaxing vascular sm ooth muscle. The inhibitory effect on the phrenic nerve-diaphragm is p robably due to the previously identified neurotoxin (paradoxin). (C) 1 998 Elsevier Science Ltd. All rights reserved.