title: Dopamine-dependent ectodomain shedding and release of epidermal growth factor in developing striatum: target-derived neurotrophic signaling (Part 2).
abstract: Epidermal growth factor (EGF) and structurally related peptides promote neuronal survival and the development of midbrain dopaminergic neurons; however, the regulation of their production has not been fully elucidated. In this study, we found that the treatment of striatal cells with dopamine agonists enhances EGF release both in vivo and in vitro. We prepared neuron-enriched and non-neuronal cell-enriched cultures from the striatum of rat embryos and challenged those with various neurotransmitters or dopamine receptor agonists. Dopamine and a dopamine D(1) -like receptor agonist (SKF38393) triggered EGF release from neuron-enriched cultures in a dose-dependent manner. A D(2) -like agonist (quinpirole) increased EGF release only from non-neuronal cell-enriched cultures. The EGF release from striatal neurons and non-neuronal cells was concomitant with ErbB1 phosphorylation and/or with the activation of a disintegrin and metalloproteinase and matrix metalloproteinase. The EGF release from neurons was attenuated by an a disintegrin and metalloproteinase/matrix metalloproteinase inhibitor, GM6001, and a calcium ion chelator, BAPTA/AM. Transfection of cultured striatal neurons with alkaline phosphatase-tagged EGF precursor cDNA confirmed that dopamine D(1) -like receptor stimulation promoted both ectodomain shedding of the precursor and EGF release. Therefore, the activation of striatal dopamine receptors induces shedding and release of EGF to provide a retrograde neurotrophic signal to midbrain dopaminergic neurons.
authors.affiliation: Molecular Neurobiology, Brain Research Institute, Niigata University, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Abe
authors.forename: Ying-Shan
authors.initials: YS
authors.lastname: Piao
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shishido
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takei
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nawa
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D051722:ADAM Proteins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019274:Botulinum Toxins, Type A / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D002614:Chelating Agents; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D005732:Gangliosides; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D011954:Receptors, Dopamine; C062875:ganglioside A2B5; D019257:Quinpirole; D004815:Epidermal Growth Factor; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D066246:ErbB Receptors; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D019274:Botulinum Toxins, Type A; D004298:Dopamine