Dopamine D(1) receptor expression in human basal ganglia and changes in Parkinson's disease.
The expression of the human dopamine D(1) receptor was examined by reverse transcription polymerase chain reaction (RT-PCR) and radioligand binding using [(3)H]-SCH23390 in post-mortem brain tissue that was obtained from normal subjects and patients dying with Parkinson's disease who were receiving treatment with dopaminergic drugs. D(1) receptor mRNA and specific [(3)H]-SCH23390 binding sites were found in both striatal (nucleus accumbens, caudate nucleus and putamen) and extrastriatal (globus pallidus and substantia nigra) brain regions. In parkinsonian brain, D(1) receptor mRNA was increased in the nucleus accumbens, while a decrease was detected in the substantia nigra pars compacta. No change in D(1) mRNA levels was found in the other brain areas examined. An increase in the density of specific [(3)H]-SCH23390 binding sites was found in the anterior putamen and a decrease in the external segment of the globus pallidus, no changes were detected elsewhere. This study demonstrates that regulation of D(1) receptor expression in the brain of patients dying with Parkinson's disease that were treated with L-DOPA is confined to small alterations in restricted brain regions.
Hurley
M J
MJ
Neurology Department, University of Miami School of Medicine, Miami, FL 31336, USA. mhurley@ich.ucl.ac.uk
Mash
D C
DC
Jenner
P
P
D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia / Q000378:metabolism*; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology; D001923:Brain Chemistry / Q000235:genetics; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D017447:Receptors, Dopamine D1 / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014316:Tritium
D001552:Benzazepines; D018492:Dopamine Antagonists; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D014316:Tritium