4.8 Article

Using Single-Cell Amperometry To Reveal How Cisplatin Treatment Modulates the Release of Catecholamine Transmitters during Exocytosis

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 55, Issue 31, Pages 9041-9044

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201602977

Keywords

amperometry; chemotherapy; cisplatin; exocytosis

Funding

  1. European Research Council
  2. Knut and Alice Wallenberg Foundation
  3. Swedish Research Council (VR)
  4. National Institutes of Health

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The pretreatment of cultured pheochromocytoma (PC12) cells with cis-diamminedichloroplatinum (cisplatin), an anti-cancer drug, influences the exocytotic ability of the cells in a dose-dependent manner. Low concentrations of cisplatin stimulate catecholamine release whereas high concentrations inhibit it. Single-cell amperometry reflects that 2 mm cisplatin treatment increases the frequency of exocytotic events and reduces their duration, whereas 100 mm cisplatin treatment decreases the frequency of exocytotic events and increases their duration. Furthermore, the stability of the initial fusion pore that is formed in the lipid membrane during exocytosis is also regulated differentially by different cisplatin concentrations. This study thus suggests that cisplatin influences exocytosis by multiple mechanisms.

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