Scorpion venom (Leiurus quinquestriatus) elicits accumulations of inositol phosphates and cyclic AMP in guinea pig cortical synaptoneurosomes.

Scorpion (Leiurus quinquestriatus) venom (ScV) stimulated accumulations of cyclic AMP and turnover of phosphatidylinositol in guinea pig cortical synaptoneurosomes. The concentrations of ScV that were necessary to increase cyclic [3H]AMP accumulation were lower than those required to stimulate formation of [3H]inositol phosphates from phosphatidylinositol. In the presence of 10 microM 2-chloroadenosine, ScV induced a dose-dependent synergistic accumulation of cyclic AMP with an EC50 value that was comparable to the EC50 required for stimulation of phosphatidylinositol turnover. Tetrodotoxin partially inhibited cyclic AMP accumulations elicited by ScV indicating that at least part of such responses are due to activation of voltage-dependent sodium channel. Tetrodotoxin virtually completely blocked formation of inositol phosphate stimulated by ScV. High concentrations of Mg2+ (30 mM) did not block responses to ScV indicating that release of neurotransmitters was not involved. Membrane potential changes could not be detected at concentrations of ScV that triggered the biochemical responses. Stimulation of phosphatidylinositol turnover by ScV appears to depend on an increase in influx of Na+ in synaptoneurosomes, presumably due to slowing of the inactivation of voltage-dependent sodium channels by alpha-scorpion toxin, a component of ScV. At least in part, the stimulation of cyclic AMP accumulation by ScV correlates with increases in phosphatidylinositol turnover.