Abstract
Ciliary neurotrophic factor and bone morphogenetic proteins induce astrocytogenesis in the developing rat brain by stimulating STAT- and Smad-dependent signaling, respectively. We previously found that stimulation of the cAMP-dependent signaling pathway also triggers differentiation of cerebral cortical precursor cells into astrocytes, providing an additional mechanism to promote astrocyte differentiation. In this study, we show that pituitary adenylate cyclase-activating polypeptide (PACAP), but not the related vasoactive intestinal peptide, induces astrocyte differentiation of cortical precursor cells, even after a transient exposure. Cortical precursors were found to express predominantly the short isoform of the PACAP-specific PAC1 receptor, which couples to adenylate cyclase. Consistent with this notion, we determined that exposure of cortical precursors to PACAP resulted in a dose-dependent increase in cAMP production. Pretreatment of cells with the cAMP antagonist Rp-cAMPS prevented astrocyte differentiation. Thus, PACAP acts as an extracellular signal to trigger cortical precursor cell differentiation into astrocytes via stimulation of intracellular cAMP production.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Animals
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / metabolism*
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Biogenic Monoamines / metabolism
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Biogenic Monoamines / pharmacology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cell Division / drug effects
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Cell Division / physiology
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / embryology*
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Cerebral Cortex / metabolism
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Cyclic AMP / metabolism*
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Dose-Response Relationship, Drug
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Fetus
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / physiology
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Glial Fibrillary Acidic Protein / drug effects
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Glial Fibrillary Acidic Protein / metabolism
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Neuropeptides / metabolism*
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Neuropeptides / pharmacology
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Protein Isoforms / drug effects
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Neurotransmitter / drug effects
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Receptors, Neurotransmitter / metabolism
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
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Receptors, Pituitary Hormone / drug effects
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Receptors, Pituitary Hormone / genetics
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Receptors, Pituitary Hormone / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Stem Cells / cytology
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Stem Cells / drug effects
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Stem Cells / metabolism*
Substances
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Adcyap1 protein, rat
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Adcyap1r1 protein, rat
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Biogenic Monoamines
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Glial Fibrillary Acidic Protein
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Neuropeptides
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Protein Isoforms
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RNA, Messenger
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Receptors, Neurotransmitter
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
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Receptors, Pituitary Hormone
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8-Bromo Cyclic Adenosine Monophosphate
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Cyclic AMP