title: Effects of erythropoietin on neuronal activity.
abstract: Recently, erythropoietin (EPO) receptors and synthesis of EPO have been identified in the brain. To clarify the effects of EPO on neuronal cells, we investigated the effects of EPO on Ca2+ uptake, intracellular Ca2+ concentration, membrane potential, cell survival, 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 45Ca2+ uptake and intracellular Ca2+ concentration in PC12 cells in a dose-related manner; these increases were inhibited by nicardipine (1 microM) or anti-EPO antibody (1:100 dilution). EPO induced membrane depolarization in PC12 cells. After a 5-day culture without serum and nerve growth factor (NGF), viable cell number decreased to 50% of that of the control cells cultured with serum and NGF. EPO (10(-13)-10(-10) M) increased the number of viable cells cultured without serum and NGF; this increase was blunted by nicardipine or anti-EPO antibody. Incubation with EPO (10(-13)-10(-10) M) stimulated mitogen-activated protein kinase activity in PC12 cells. EPO (10(-13)-10(-10) M) increased dopamine release from PC12 cells and tyrosine hydroxylase activity; these increases were sensitive to nicardipine or anti-EPO antibody. Following a 4-h incubation with EPO (10(-14)-10(-10) M), NO production was increased, which was blunted by nicardipine and anti-EPO antibody. In contrast, maximal NO synthase activity was not changed by EPO. These results suggest that EPO stimulates neuronal function and viability via activation of Ca2+ channels.
authors.affiliation: Department of Medicine, Shimane Medical University, Izumo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Koshimura
authors.forename: Y
authors.initials: Y
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Sohmiya
authors.forename: J
authors.initials: J
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004921:Erythropoietin / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000906:Antibodies; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D004921:Erythropoietin; D009569:Nitric Oxide; D009529:Nicardipine; D014446:Tyrosine 3-Monooxygenase; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium; D004298:Dopamine