title: Stimulation of suicidal erythrocyte death by amantadine.
abstract: Amantadine is an effective drug for treatment of both, Parkinson's disease and viral infections. Side effects of amantadine include anemia, which may limit its therapeutic use. The cause of amantatine induced anemia is ill defined. At least in theory, the anemia could partially result from suicidal erythrocyte death or eryptosis, which accelerates the clearance of circulating erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Triggers of erythrocyte membrane scrambling include an increase of cytosolic Ca2+ concentration ([Ca2+]i) resulting from activation of Ca2+-permeable cation channels. The present study has been performed to test for an effect of amantadine on eryptosis. Erythrocytes from healthy volunteers were exposed to amantadine and annexin V binding (disclosing phosphatidylserine exposure), forward scatter (reflecting cell volume), and Fluo3-dependent fluorescence (reflecting [Ca2+]i) were determined by flow cytometry. Exposure of erythrocytes to amantadine (> or =0.2 microg/ml) increased [Ca2+]i and triggered annexin V binding, and increased forward scatter. The effect on annexin V binding was virtually abolished in the absence of extracellular Ca2+. The present observations disclose mechanisms presumably contributing to amantadine induced anemia.
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Corinna
authors.initials: C
authors.lastname: Geiger
authors.forename: Hasan
authors.initials: H
authors.lastname: Mahmud
authors.forename: Jan
authors.initials: J
authors.lastname: Nicolay
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000547:Amantadine / Q000633:toxicity*; D000740:Anemia / Q000139:chemically induced*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010718:Phosphatidylserines / Q000378:metabolism
chemical_list: D017304:Annexin A5; D010718:Phosphatidylserines; D000547:Amantadine; D002118:Calcium