title: Erythropoietin inhibits calcium-induced neurotransmitter release from clonal neuronal cells.
abstract: Erythropoietin (EPO) and EPO receptor (EPO-R) are expressed in the brain but their neuronal functions are not yet clarified. The effects of EPO on neurosecretion were studied using clonal rat pheochromocytoma PC12 cells. EPO suppressed Ca(2+)-induced dopamine release from PC12 cells in a concentration- and time-dependent manner. Inhibition was also produced by an EPO mimetic peptide 1 (EMP1), a small synthetic peptide agonist of EPO-R, but not by its inactive analogue in which Cys residues were substituted with Ser. Inhibition was abolished by genistein but not by genistin. EPO and EMP1 induced autophosphorylation of Janus kinase 2 (JAK 2), a tyrosine kinase that associates with EPO-R, and dephosphorylation of GAP-43 in a tyrosine kinase-dependent fashion. These results suggest that EPO suppresses neurotransmitter release through activation of EPO-R linked to JAK2.
authors: Department of Life Sciences (Biology), Graduate School of Arts and Sciences, University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
authors: M
authors: M
authors: Kawakami
authors: S
authors: S
authors: Iwasaki
authors: K
authors: K
authors: Sato
authors: M
authors: M
authors: Takahashi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004789:Enzyme Activation; D004921:Erythropoietin / Q000494:pharmacology*; D053614:Janus Kinase 2; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D051381:Rats; D017467:Receptors, Erythropoietin / Q000378:metabolism
chemical_list: D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D002118:Calcium; D004298:Dopamine