Prejunctional effects of a purified toxin from the scorpion Tityus serrulatus: release of 3H-noradrenaline and enhancement of transmitter overflow elicited by nerve stimulation

Abstract

The effects of a purified fraction of the venom of the Brazilian scorpion, Tityus serrulatus, were studied in isolated guinea-pig atria previously labelled with 3H-noradrenaline. Exposure to 0.3 and 1.0 mug/ml of the scorpion toxin resulted in a long lasting positive chronotropic effect which was concentration-dependent. The increase in atrial rate coincided with an enhancement in spontaneous outflow of radioactivity. The increase in outflow of radioactive products elicited by exposure to 1.0 mug/ml of the scorpion toxin was approximately 3-fold. 3H-noradrenaline accounted for 60% of the total increase in outflow of radioactivity elicited by the scorpion toxin and the 3H-deaminated glycol (3,4-dihydroxyphenyl-glycol) represented the main metabolite formed, accounting for approximately 35% of the total release. 20 min after exposure to 1.0 mug/ml of the scorpion toxin the overflow of the labelled transmitter elicited by accelerans nerve stimulation (4 Hz, during 60 sec. supramaximal voltage) was increased 8-fold. This effect of the scorpion toxin appears to be unrelated to inhibition of neuronal uptake, block of alpha-adrenoceptors or stimulation of beta-adrenoceptors. Consequently, in addition to releasing noradrenaline, the scorpion toxin enhances transmitter overflow elicited by nerve stimulation through a prejunctional effect which appears to reflect a nove mechanism of action.