title: Opioid-induced proliferation through the MAPK pathway in cultures of adult hippocampal progenitors.
abstract: Administration of opioid agonists or antagonists has been reported to regulate proliferation or survival of neural progenitors in vivo. Here we report that beta-endorphin and selective mu-opioid receptor (MOR) and delta-opioid receptor (DOR) agonists stimulate proliferation of isolated rat adult hippocampal progenitors (AHPs). The AHPs were found to express DORs and MORs, but not kappa-opioid receptors. Incubation with beta-endorphin for 48 h increased the number of AHPs found in mitosis, the total DNA content, and the expression of proliferating cell nuclear antigen. This proliferative effect from beta-endorphin on AHPs was antagonized by naloxone. The beta-endorphin-induced proliferation was mediated through phosphorylation of extracellular signal-regulated kinases 1 and 2 and dependent on phosphatidylinositol 3-kinase and both intra- and extracellular calcium. These data suggest a role for the opioid system in the regulation of proliferation in progenitors from the adult hippocampus.
authors.affiliation: The Arvid Carlsson Institute for Neuroscience at Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.
authors.forename: Anders I
authors.initials: AI
authors.lastname: Persson
authors.forename: Thorleif
authors.initials: T
authors.lastname: Thorlin
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bull
authors.forename: Peter S
authors.initials: PS
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D001615:beta-Endorphin / Q000494:pharmacology*
chemical_list: D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium