Calcium in suramin-induced rat sensory neuron toxicity in vitro

Suramin is an experimental chemotherapeutic agent and a neurotoxin which causes a dose-dependent peripheral neuropathy in vivo and inhibits dorsal root ganglion (DRG) neurite outgrowth in vitro. The mechanism of suramin-induced cyto- and neurotoxicity remains unclear. Calcium is a key signal transducer in cellular responses to a variety of physiological and pathogenic stimuli. In the present study, we have determined the role of calcium in suramin-induced neurotoxicity in dorsal root ganglion neurons in vitro. Suramin-induced inhibition of neurite outgrowth and induction of neuronal cell death were dose-related phenomena. A low level of extracellular calcium significantly reduced suramin-induced inhibition of neurite outgrowth and delayed neuronal cell death in vitro. Nimodipine (100 microM), an L-type voltage-sensitive calcium channel (VSCC) inhibitor, mimicked low calcium medium and protected neurite outgrowth in regular calcium medium supplemented with 300 microM suramin. TMB-8 (100 microM), an inhibitor of intracellular calcium release, failed to protect neurite outgrowth against the toxin. Calmidazolium (10 microM), a potent calmodulin inhibitor, and calpain inhibitor peptide (CIP, 10 microM) protected neurite outgrowth against suramin. The results support the hypothesis that the calcium signaling system is important in suramin-induced neurotoxicity. Influx of extracellular calcium is more important than release of intracellular calcium in causing cell injury in vitro.