Cellular signaling in PC12 affected by pardaxin

Pardaxins, a family of polypeptide, excitatory neurotoxins, isolated from the gland's secretion of Pardachirus fish are used as pharmacological tools to investigate calcium-dependent and calcium-independent signaling leading to neurotransmitter release. In PC12 cells, a neural model to study exocytosis, pardaxin forms voltage-dependent pores which are involved in pardaxin-induced increase in intracellular calcium and calcium-dependent dopamine release. Pardaxin-induced calcium-independent, dopamine release from PC12 cells is attributed to the stimulation of the arachidonic acid cascade and the increased release of the arachidonic acid metabolites produced by the lipoxygenase pathways. Pardaxin rapidly stimulates MAPK phosphorylation activity, which is proposed to be involved in pardaxin-induced arachidonic acid and dopamine release. It seems likely that pardaxin delayed stimulation of stress-kinases JNK and p38 will play a prominent role in triggering cell death. Collectively, these results demonstrate that pardaxin selectively modulates neuronal signaling to achieve massive exocytosis and neurotoxicity.