| Autocrine expression and ontogenetic functions of the PACAP ligand/receptor system during sympathetic development. | |
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MedLine Citation:
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PMID: 10694416 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The superior cervical ganglion (SCG) is a well-characterized model of neural development, in which several regulatory signals have been identified. Vasoactive intestinal peptide (VIP) has been found to regulate diverse ontogenetic processes in sympathetics, though functional requirements for high peptide concentrations suggest that other ligands are involved. We now describe expression and functions of pituitary adenylate cyclase-activating polypeptide (PACAP) during SCG ontogeny, suggesting that the peptide plays critical roles in neurogenesis. PACAP and PACAP receptor (PAC(1)) mRNA's were detected at embryonic days 14.5 (E14.5) through E17.5 in vivo and virtually all precursors exhibited ligand and receptor, indicating that the system is expressed as neuroblasts proliferate. Exposure of cultured precursors to PACAP peptides, containing 27 or 38 residues, increased mitogenic activity 4-fold. Significantly, PACAP was 1000-fold more potent than VIP and a highly potent and selective antagonist entirely blocked effects of micromolar VIP, consistent with both peptides acting via PAC(1) receptors. Moreover, PACAP potently enhanced precursor survival more than 2-fold, suggesting that previously defined VIP effects were mediated via PAC(1) receptors and that PACAP is the more significant developmental signal. In addition to neurogenesis, PACAP promoted neuronal differentiation, increasing neurite outgrowth 4-fold and enhancing expression of neurotrophin receptors trkC and trkA. Since PACAP potently activated cAMP and PI pathways and increased intracellular Ca(2+), the peptide may interact with other developmental signals. PACAP stimulation of precursor mitosis, survival, and trk receptor expression suggests that the signaling system plays a critical autocrine role during sympathetic neurogenesis. |
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Authors:
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E DiCicco-Bloom; P J Deutsch; J Maltzman; J Zhang; J E Pintar; J Zheng; W F Friedman; X Zhou; T Zaremba |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Developmental biology Volume: 219 ISSN: 0012-1606 ISO Abbreviation: Dev. Biol. Publication Date: 2000 Mar |
Date Detail:
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Created Date: 2000-04-03 Completed Date: 2000-04-03 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0372762 Medline TA: Dev Biol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 197-213 Citation Subset: IM |
Copyright Information:
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Copyright 2000 Academic Press. |
Affiliation:
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Department of Neuroscience, UMDNJ/Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Survival / drug effects Cells, Cultured Cyclic AMP / metabolism DNA / biosynthesis Gene Expression Regulation, Developmental Ligands Mitosis / drug effects Neurites / drug effects Neuropeptides / genetics, metabolism*, pharmacology Pituitary Adenylate Cyclase-Activating Polypeptide RNA, Messenger / genetics, metabolism Rats Receptor, trkA / metabolism Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide Receptors, Pituitary Hormone / genetics, metabolism* Second Messenger Systems Superior Cervical Ganglion / drug effects, embryology, metabolism Sympathetic Nervous System / drug effects, embryology*, metabolism* Vasoactive Intestinal Peptide / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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DA08622/DA/NIDA NIH HHS; MH-AG19957/MH/NIMH NIH HHS; NS32401/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adcyap1 protein, rat; 0/Ligands; 0/Neuropeptides; 0/Pituitary Adenylate Cyclase-Activating Polypeptide; 0/RNA, Messenger; 0/Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; 0/Receptors, Pituitary Hormone; 37221-79-7/Vasoactive Intestinal Peptide; 60-92-4/Cyclic AMP; 9007-49-2/DNA; EC 2.7.10.1/Receptor, trkA |
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