Prejunctional action of the venom from the Indian red scorpion Mesobuthus tamulus on adrenergic transmission in vitro

Abstract

Venom (RSV) from the Indian red scorpion, Mesobuthus tamulus (Buthus tamulus), can cause increased peripheral sympathetic activity with consequent enhancement of adrenergic responses. We have therefore investigated the effects of RSV on adrenergic transmission in the rat isolated anococcygeus muscle. The effects of phentolamine (5 μM), tetrodotoxin (2 μM), guanethidine (5 μM), desipramine (1 μM) and reserpine pretreatment in vivo (5 mg/kg s.c. x 24 hr and 5 mg/kg i.p. x 3 hr) on the contractile responses of the rat anococcygeus muscle to RSV (1.5 μg/ml), field stimulation, noradrenaline (NA, 1 μM or 3 μM) and tyramine (15 μM) were compared. The contractile responses to RSV and to field stimulation were completely blocked by phentolamine, tetrodotoxin, guanethidine and reserpine pretreatment, but the responses were potentiated by desipramine. The contractile responses to tyramine were completely blocked by phentolamine, reserpine pretreatment as well as desipramine. The responses to NA were completely blocked by phentolamine, but were potentiated by guanethidine, desipramine and reserpine. Relatively low concentrations (0.1 μg/ml x 4) of RSV which did not produce any observable increase in tone of the anococcygeus muscle, potentiated the contractile responses of the anococcygeus muscle to field stimulation, but not the responses to exogenous NA; 4-aminopyridine (25 μM x 2) also potentiated the muscle responses to field stimulation. HPLC measurements revealed only ver low concentrations (0.10 ± 0.03 μmol/g venom) of NA in RSV. Thus, the adrenergic agonist action of RSV in the rat isolated anococcygeus muscle can be attributed to the involvement of some prejunctional mechanism(s) of action that stimulates the release of neurotransmitter which differs from the indirect action mediated by tyramine.