Effect of cisplatin on dopamine release from PC12 cells.
The effect of cisplatin, carboplatin and cyclophosphamide treatments on the neurotransmitter release process and the changes in intracellular Ca2+ level was determined by using PC12 cell experimental model. The neurotransmitter releasing ability of selected anticancer drugs was assessed by estimating the amount of dopamine release induced by them from PC12 cells. Among the three anticancer drugs tested in this study, cisplatin induced a maximum release of dopamine from PC12 cells. In addition, cisplatin pretreatment significantly increased the dopamine release stimulated by carbachol (0.5 mM) and KCl (55 mM). The additive effect exerted by cisplatin over KCl (55 mM) induced dopamine release was effectively blocked by verapamil (10 microM). The intracellular Ca2+ studies performed with cisplatin, carbachol and KCl (55 mM) treatments indicated that cisplatin does not induce any changes in the intracellular Ca2+ levels on its own, however it potentiates the effect of carbachol and KCl. Our study suggests that PC12 cells can be used as an experimental model to test the neurotransmitter releasing ability of emetic anticancer drugs.
Kasabdji
D
D
Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Ft. Lauderdale, FL 33328, USA.
Shanmugam
V
V
Rathinavelu
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D016190:Carboplatin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D016716:PC12 Cells; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D014700:Verapamil / Q000494:pharmacology
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011189:Potassium Chloride; D001285:Atropine; D003520:Cyclophosphamide; D002217:Carbachol; D016190:Carboplatin; D014700:Verapamil; D002945:Cisplatin; D002118:Calcium; D004298:Dopamine