Some pharmacological studies of venom from the inland taipan (Oxyuranus microlepidotus).
The present study was designed to obtain a basic pharmacological profile of venom from the inland taipan (Oxyuranus microlepidotus). Venom (0.05-50 micrograms/ml) produced dose-dependent contractions in guinea-pig ileum, which could not be reproduced upon second administration. The cyclooxygenase inhibitor indomethacin (1 microM), a preceding anaphylactic response induced by egg albumin and inactivation of phospholipase A2 (PLA2) by incubation with 4-bromophenacyl bromide (1.8 mM) all significantly inhibited responses to venom (0.5 micrograms/ml). Venom (0.5 micrograms/ml) caused inhibition of stimulation-induced contractions in the prostatic segment of rat vas deferens which was not significantly affected by the alpha 2-adrenoceptor antagonist idazoxan (0.3 microM). Venom (10 micrograms/ml) caused time-dependent inhibition of the rat electrically stimulated phrenic nerve-diaphragm preparation, positive inotropic and chronotropic responses in rat isolated atria and relaxation in rat endothelium-denuded and -intact isolated aortae. In endothelium-intact aortae, the nitric oxide synthase inhibitor N-nitro-L-arginine (NOLA, 0.1 mM) significantly inhibited the response to venom (10 micrograms/ml). Venom (50 micrograms/kg, i.v.) caused an immediate drop in blood pressure followed by cardiovascular collapse in anaesthetised rats. Venom (10 micrograms/kg, i.v.) caused a gradual fall in blood pressure which was sometimes accompanied by a temporary cessation of respiration. A PLA2 assay detected the presence of PLA2 in the venom. These results suggest that the venom contains a component capable of causing the synthesis of arachidonic acid metabolites and a component capable of relaxing vascular smooth muscle. The inhibitory effect on the phrenic nerve-diaphragm is probably due to the previously identified neurotoxin (paradoxin).
Bell
K L
KL
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Sutherland
S K
SK
Hodgson
W C
WC
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003964:Diaphragm / Q000187:drug effects; D004546:Elapid Venoms / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D010791:Phrenic Nerve / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014649:Vas Deferens / Q000187:drug effects
D004546:Elapid Venoms