Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-3-28
pubmed:abstractText
The dopamine D4 receptor has been investigated for its potential role in several CNS disorders, notably schizophrenia and more recently, erectile dysfunction. Whereas studies have investigated dopamine D4 receptor-mediated signaling in vitro, there have been few, if any, attempts to identify dopamine D4 receptor signal transduction pathways in vivo. In the present studies, the selective dopamine D4 agonist PD168077 induces c-Fos expression and extracellular signal regulated kinase (ERK) phosphorylation in the hypothalamic paraventricular nucleus (PVN), a site known to regulate proerectile activity. The selective dopamine D4 receptor antagonist A-381393 blocked both c-Fos expression and ERK1/2 phosphorylation produced by PD168077. In addition, PD168077-induced ERK1/2 phosphorylation was prevented by SL327, an inhibitor of ERK1/2 phosphorylation. Interestingly, treatment with A-381393 alone significantly reduced the amount of Fos immunoreactivity as compared to basal expression observed in vehicle-treated controls. Dopamine D4 receptor and c-Fos coexpression in the PVN was observed using double immunohistochemical labeling, suggesting that PD168077-induced signaling may result from direct dopamine D4 receptor activation. Our results demonstrate functional dopamine D4 receptor expression and natural coupling in the PVN linked to signal transduction pathways that include immediate early gene and MAP kinase activation. Further, the ability of the selective dopamine D4 antagonist A-381393 alone to reduce c-Fos expression below control levels may imply the presence of a tonic dopamine D4 receptor activation under basal conditions in vivo. These findings provide additional evidence that the PVN may be a site of dopamine D4 receptor-mediated proerectile activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
521-31
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16324724-Aminoacetonitrile, pubmed-meshheading:16324724-Animals, pubmed-meshheading:16324724-Benzamides, pubmed-meshheading:16324724-Benzimidazoles, pubmed-meshheading:16324724-Cell Count, pubmed-meshheading:16324724-Dose-Response Relationship, Drug, pubmed-meshheading:16324724-Drug Interactions, pubmed-meshheading:16324724-Enzyme Inhibitors, pubmed-meshheading:16324724-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:16324724-Gene Expression, pubmed-meshheading:16324724-Genes, fos, pubmed-meshheading:16324724-Immunohistochemistry, pubmed-meshheading:16324724-Male, pubmed-meshheading:16324724-Paraventricular Hypothalamic Nucleus, pubmed-meshheading:16324724-Phosphorylation, pubmed-meshheading:16324724-Piperazines, pubmed-meshheading:16324724-Rats, pubmed-meshheading:16324724-Rats, Sprague-Dawley, pubmed-meshheading:16324724-Receptors, Dopamine D4, pubmed-meshheading:16324724-Signal Transduction, pubmed-meshheading:16324724-Time Factors
pubmed:year
2006
pubmed:articleTitle
Dopamine D4 receptor signaling in the rat paraventricular hypothalamic nucleus: Evidence of natural coupling involving immediate early gene induction and mitogen activated protein kinase phosphorylation.
pubmed:affiliation
Abbott Laboratories, Neuroscience Research, Abbott Park, IL 60064-3500, USA. robert.s.bitner@abbott.com
pubmed:publicationType
Journal Article, Comparative Study