Linked Life Data

12122070

Source:http://linkedlifedata.com/resource/pubmed/id/12122070

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2002-7-17
pubmed:abstractText
This study addresses the hypothesis that the previously described capacity of D1 dopamine receptors (D1Rs) to regulate dendritic growth in developing cortical neurons may involve alterations in the phosphorylation state of microtubule-associated protein-2 (MAP2). The changes in phosphorylation of this protein are known to affect its ability to stabilize the dendritic cytoskeleton. The study involved two systems: primary cultures of mouse cortical neurons grown in the presence of the D1R agonists, SKF82958 or A77636, and the cortex of neonatal transgenic mice overexpressing the D1A subtype of D1R. In both models, a decrease in dendritic extension corresponded with an elevation in MAP2 phosphorylation. This phosphorylation occurred on all three amino acid residues examined in this study: serine, threonine, and tyrosine. In cultured cortical neurons, D1R stimulation-induced increase in MAP2 phosphorylation was blocked by the protein kinase A (PKA) inhibitor, H-89, and mimicked by the PKA activator, S(p)-cAMPS. This indicates that D1Rs modulate MAP2 phosphorylation through PKA-associated intracellular signaling pathways. We also observed that the elevations in MAP2 phosphorylation in neuronal cultures in the presence of D1R agonists (or S(p)-cAMPS) were maintained for a prolonged time (up to at least 96 hr). Moreover, MAP2 phosphorylation underwent a substantial increase between 24 and 72 hr of exposure to these drugs. Our findings are consistent with the idea that D1Rs can modulate growth and maintenance of dendrites in developing cortical cells by regulating the phosphorylation of MAP2. In addition, our observations suggest that MAP2 phosphorylation by long-term activation of D1Rs (and PKA) can be divided into two phases: the initial approximately 24-hr-long phase of a relatively weak elevation in phosphorylation and the delayed phase of a much more robust phosphorylation increase taking place during the next approximately 48 hr.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6092-105
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12122070-Animals, pubmed-meshheading:12122070-Animals, Newborn, pubmed-meshheading:12122070-Cells, Cultured, pubmed-meshheading:12122070-Cerebral Cortex, pubmed-meshheading:12122070-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:12122070-Dendrites, pubmed-meshheading:12122070-Dopamine Agonists, pubmed-meshheading:12122070-Dose-Response Relationship, Drug, pubmed-meshheading:12122070-Enzyme Activators, pubmed-meshheading:12122070-Enzyme Inhibitors, pubmed-meshheading:12122070-Frontal Lobe, pubmed-meshheading:12122070-Mice, pubmed-meshheading:12122070-Mice, Transgenic, pubmed-meshheading:12122070-Microtubule-Associated Proteins, pubmed-meshheading:12122070-Neurites, pubmed-meshheading:12122070-Neurons, pubmed-meshheading:12122070-Phosphorylation, pubmed-meshheading:12122070-Receptors, Dopamine D1, pubmed-meshheading:12122070-Serine, pubmed-meshheading:12122070-Signal Transduction, pubmed-meshheading:12122070-Threonine, pubmed-meshheading:12122070-Time Factors, pubmed-meshheading:12122070-Tyrosine
pubmed:year
2002
pubmed:articleTitle
D1 dopamine receptor regulation of microtubule-associated protein-2 phosphorylation in developing cerebral cortical neurons.
pubmed:affiliation
Department of Oral and Craniofacial Biological Sciences, University of Maryland, Baltimore, Maryland 21201, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't