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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium / metabolism
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Cell Division / drug effects
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Cells, Cultured
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Female
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Hippocampus / cytology*
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In Vitro Techniques
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MAP Kinase Signaling System / drug effects
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MAP Kinase Signaling System / physiology*
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism
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Neurons / cytology*
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Neurons / drug effects
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Neurons / metabolism
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Pertussis Toxin / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation / drug effects
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Rats
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Rats, Inbred F344
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, kappa / agonists
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Receptors, Opioid, mu / agonists
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Stem Cells / cytology*
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Stem Cells / metabolism
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beta-Endorphin / pharmacology*
Substances
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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beta-Endorphin
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Pertussis Toxin
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Phosphatidylinositol 3-Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Calcium