Gyroxin fails to modify in vitro release of labelled dopamine and acetylcholine from rat and mouse striatal tissue

Gyroxin fails to modify in vitro release of labelled dopamine and acetylcholine from rat and mouse striatal tissue. Gyroxin is a thrombin-like peptide with amidasic, esterasic and fibrinogenolitic activities, found in the venom of snakes like Lachesis muta muta and Crotalus durissus terrificus. Intravenous injections of small doses of gyroxin induce a typical barrel rotation behaviour that has been thought to be a neurotoxic effect. The aim of this study was to determine whether gyroxin-induced barrel rotation behaviour involves changes in neurotransmitter release. Gyroxin was isolated from crude venoms by gel filtration and affinity chromatography. Its properties were determined by assaying esterasic, amidasic and fibrinogenolitic enzymatic activities and tested for barrel rotation behaviour. Neurotransmitter release tests employed rat and mouse superfused brain striatal chopped tissue preloaded with [H-3]-dopamine, [H-3]-acetylcholine or in a double labelling procedure. They were stimulated by 20 mM K+ in control conditions or in the presence of several concentrations of toxins. Crotoxin and crotamine were used as positive controls. Gyroxins failed at modifying both basal and stimulated neurotransmitter releases, suggesting a lack of direct neurotoxic effect. We therefore suggest that gyroxin may not be a neurotoxin but rather, induces this behavioural syndrome by other means possibly related to haemodynamic disturbance. The possible role of vasopressin is discussed. (C) 2001 Elsevier Science Ltd. All rights reserved.