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Endothelin-3 stimulates inositol 1,4,5-trisphosphate production and Ca2+ influx to produce biphasic dopamine release from rat striatal slices

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Summary

1. Real-time monitoring of dopamine (DA) release from rat striatal slices demonstrated that endothelin (ET)-3 (0.1–10μM) produced a biphasic DA release consisting of transient and sustained components. When extracellular Ca2+ was removed, the sustained but not transient response remarkably decreased.

2. ET-3 (1–10μM) stimulated an increase in the intracellular Ca2+ concentration ([Ca2+]i), which also consisted of two components. The external Ca2+ depletion inhibited primarily the sustained component of the Ca2+ response to ET-3.

3. ET-3 increased inositol 1,4,5-trisphosphate (IP3) concentrations in striatal slices. This response peaked at 10 to 20 sec and returned to the basal level 2 min after stimulation, an event which was in good accord with a prompt and transient phase of both cytosolic Ca2+ activity and DA release evoked by ET-3.

4. Thus, ET-3 produces a transient and a sustained release of DA from striatal slices by stimulating intracellular Ca2+ mobilization via IP3 formation and extracellular Ca2+ influx, respectively.

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Kataoka, Y., Koizumi, S., Niwa, M. et al. Endothelin-3 stimulates inositol 1,4,5-trisphosphate production and Ca2+ influx to produce biphasic dopamine release from rat striatal slices. Cell Mol Neurobiol 14, 271–280 (1994). https://doi.org/10.1007/BF02088325

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