Functional interaction between dopamine receptor subtypes for the regulation of c-fos expression.
Dopaminergic drugs increase the expression of the proto-oncogene, c-fos, in the brain, which is involved in the coordination of neurobiological changes caused by repeated cocaine or amphetamine use. This study examined the roles of five dopamine receptor subtypes on the c-fos promoter activity. D(1)R or D(5)R significantly increased the expression of c-fos promoter by activating protein kinase A. However, D(2)R, D(3)R, or D(4)R did not show any noticeable effects. The co-expression of D(1)R/D(3)R or D(1)R/D(2)R synergistically activated the basal and agonist-induced expression of the c-fos promoter, respectively. The Ral guanine-nucleotide-dissociation-stimulator-like, which was found to interact with the 3rd cytoplasmic loop of D(3)R, mediated the inhibitory activity of D(3)R in c-fos expression. In summary, the expression of the c-fos promoter was increased by the D1-like receptors and enhanced synergistically by the D2-like receptors via the modulation of cellular cAMP. D(3)R inhibited the expression of the c-fos promoter through an interaction with RGL.
Cho
Dong-Im
DI
Research Institute of Drug Development, College of Pharmacy, Chonnam National University, Kwang-Ju 500-757, Republic of Korea.
Quan
WenYing
W
Oak
Min-Ho
MH
Choi
Hyun Jin
HJ
Lee
Kwang Youl
KY
Kim
Kyeong-Man
KM
D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011954:Receptors, Dopamine; D051076:Proto-Oncogene Proteins c-fyn