D1 receptor regulation of preprotachykinin-A gene by extracellular signal-regulated kinase pathway in striatal cultures.
In animal models of Parkinson's disease, a supersensitive response to dopamine (DA) is associated with a switch in the coupling of striatal DA D1 receptors from a cyclic AMP/protein kinase A signaling pathway to one involving extracellular signal-regulated kinase/mitogen-associated protein kinase. In this study, we found that generation of organotypic striatal cultures, with concomitant loss of DA innervation, led to a downregulation in preprotachykinin-A gene expression, which was reinstated by D1 receptor activation in an extracellular signal-regulated kinase/mitogen-associated protein kinase-dependent manner. These data demonstrate that acute organotypic slice cultures recapitulate important changes in D1 receptor-mediated signal transduction seen in DA-denervated animals, providing a valuable model system to study denervation effects on DA signaling and striatal gene expression.
Sin
Mihaela
M
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Michelhaugh
Sharon K
SK
Bannon
Michael J
MJ
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D015536:Down-Regulation / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011498:Protein Precursors / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D015320:Tachykinins / Q000235:genetics*
D018491:Dopamine Agonists; D011498:Protein Precursors; D017447:Receptors, Dopamine D1; D015320:Tachykinins; C044206:preprotachykinin; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D004298:Dopamine