Toosendanin, a
triterpenoid from Melia toosendan Sieb et Zucc, has been found before to be an effective anti-
botulism agent, with a bi-phasic effect at both motor nerve endings and central synapse: an initial facilitation followed by prolonged depression. Initial facilitation may be due to activation of
voltage-dependent calcium channels plus inhibition of
potassium channels, but the depression is not fully understood.
Toosendanin has no effect on intracellular
calcium or secretion in the non-excitable pancreatic acinar cells, ruling out general
toosendanin inhibition of exocytosis. In this study,
toosendanin effects on sensory neurons isolated from rat nodose ganglia were investigated. It was found that
toosendanin stimulated increases in cytosolic
calcium and neuronal exocytosis dose dependently. Experiments with membrane potential
indicator bis-(1,3-dibutylbarbituric acid)trimethine oxonol found that
toosendanin hyperpolarized
capsaicin-insensitive but depolarized
capsaicin-sensitive neurons; high
potassium-induced
calcium increase was much smaller in hyperpolarizing neurons than in depolarizing neurons, whereas no difference was found for
potassium-induced depolarization in these two types of neurons. In neurons showing spontaneous calcium oscillations,
toosendanin increased the oscillatory amplitude but not frequency.
Toosendanin-induced
calcium increase was decreased in
calcium-free
buffer, by
nifedipine, and by transient receptor potential vanilloid 1 (TRPV1) antagonist
capsazepine. Simultaneous measurements of cytosolic and endoplasmic reticulum (ER)
calcium showed an increase in cytosolic but a decrease in ER
calcium, indicating that
toosendanin triggered ER
calcium release. These data together indicate that
toosendanin modulates sensory neurons, but had opposite effects on membrane potential depending on the presence or absence of
capsaicin receptor/TRPV 1 channel.