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Effects of Erythropoietin on Neuronal Activity
Author(s) -
Koshimura Kunio,
Murakami Yoshio,
Sohmiya Motoi,
Tanaka Junko,
Kato Yuzuru
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722565.x
Subject(s) - erythropoietin , neuroscience , chemistry , pharmacology , medicine , biology
Recently, erythropoietin (EPO) receptors and synthesis ofEPO have been identified in the brain. To clarify the effects of EPO onneuronal cells, we investigated the effects of EPO on Ca 2+ uptake,intracellular Ca 2+ concentration, membrane potential, cellsurvival, release and biosynthesis of dopamine, and nitric oxide (NO)production in differentiated PC12 cells, which possess EPO receptors. EPO(10 ‐12 ‐10 ‐10 M ) increased 45 Ca 2+ uptake and intracellular Ca 2+ concentration in PC12 cells in a dose‐related manner; these increases wereinhibited by nicardipine (1 μ M ) or anti‐EPO antibody (1:100dilution). EPO induced membrane depolarization in PC12 cells. After a 5‐dayculture without serum and nerve growth factor (NGF), viable cell numberdecreased to 50% of that of the control cells cultured with serum and NGF. EPO(10 ‐13 ‐10 ‐10 M ) increased the number of viablecells cultured without serum and NGF; this increase was blunted by nicardipineor anti‐EPO antibody. Incubation with EPO (10 ‐13 ‐10 ‐10 M ) stimulated mitogen‐activated protein kinase activity in PC12cells. EPO (10 ‐13 ‐10 ‐10 M ) increased dopaminerelease from PC12 cells and tyrosine hydroxylase activity; these increaseswere sensitive to nicardipine or anti‐EPO antibody. Following a 4‐h incubationwith EPO (10 ‐14 ‐10 ‐10 M ), NO production wasincreased, which was blunted by nicardipine and anti‐EPO antibody. Incontrast, maximal NO synthase activity was not changed by EPO. These resultssuggest that EPO stimulates neuronal function and viability via activation ofCa 2+ channels.