Pharmacological characterization of the presynaptic activity of Tityus serrulatus venom in the rat anococcygeus muscle

Scorpion venoms are known to cause peripheral nerve stimulation with enhanced autonomic responses. This study, therefore, examined the effects of Tityus serrulatus venom (TSV) on adrenergic, cholinergic and nitrergic nerve fibers using the rat anococcygeus muscle. The contractile effects of TSV (1 μg/ml) and electrical field stimulation were markedly reduced by phentolamine (5 μM), prazosin (0.1 μM), guanethidine (30 μM) and tetrodotoxin (TTX, 1 μM), whereas imipramine (3 μM) enhanced these responses. The responses to tyramine (10 μM) were partially reduced by guanethidine and completely blocked by phentolamine, prazosin and imipramine. Atropine (1 μM) fully prevented carbachol (CCh, 30 μM)-induced contractions without affecting those mediated by TSV. Neostigmine significantly potentiated TSV-and ACh-evoked contractions, whereas hexamethonium had no effect. The relaxant responses induced by EFS and TSV (3 μg/ml) were completely blocked by l-NAME (100 μM), ODQ (1 μM) or TTX (1 μM). Addition of l-arginine (1 mM) reversed the effect of l-NAME. Thus, the motor and inhibitory responses of TSV in the rat anococcygeus muscle are mediated by prejunctional mechanisms dependent on Na+ channel activation, causing the stimulation of NA and NO release from adrenergic and nitrergic nerve fibers, respectively.