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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-7-20
pubmed:abstractText
Agonist stimulated [35S]guanosine 5'-gamma-thiotriphosphate ([35S]GTPgammaS) binding autoradiography was established for the examination of dopamine-D2/D2 receptors in human brain sections. The distribution of G proteins activated by dopamine-D2/D3 receptors was studied in whole hemisphere cryosections. Dopamine stimulated [35S]GTPgammaS binding in brain regions with high densities of dopamine D2-like receptors, i.e. putamen (23 +/- 2%, mean +/- SEM,% stimulation over basal binding), caudate (20 +/- 0%) and substantia nigra (22 +/- 2%), but also in regions with lower receptor densities such as amygdala (17 +/- 8%), hippocampus (16 +/- 6%), anterior cingulate (13 +/- 3%), and thalamus (12 +/- 2%). Dopamine stimulated [35S]GTPgammaS binding to significantly higher levels in the dorsal than in the ventral part of the striatum. Dopamine caused low or very low stimulation in all cortical areas. Raclopride, a selective D2/D3 receptor antagonist, potently inhibited dopamine stimulated [35S]GTPgammaS binding, whereas R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390), a selective D1 antagonist, did not block the [35S]GTPgammaS binding response stimulated by dopamine. Hence, the stimulatory effect of dopamine was primarily mediated by D2/D3 receptors. Quinpirole stimulated [35S]GTPgammaS binding in the same regions as dopamine. The maximal level of stimulation induced by dopamine and quinpirole was not significantly different. The present study demonstrates that agonist stimulated [35S]GTPgammaS binding autoradiography could be a suitable technique for the examination of dopamine-D2/D3 receptors in the human brain. This functional assay could provide useful new information about dopamine receptor/G protein coupling in the postmortem human brain, and reveal possible disease related alterations of the interaction between D2/D3 receptors and G proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
65-71
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16029196-Adult, pubmed-meshheading:16029196-Aged, pubmed-meshheading:16029196-Autoradiography, pubmed-meshheading:16029196-Binding, Competitive, pubmed-meshheading:16029196-Brain, pubmed-meshheading:16029196-Brain Mapping, pubmed-meshheading:16029196-Dopamine, pubmed-meshheading:16029196-Dopamine Agonists, pubmed-meshheading:16029196-Dopamine Antagonists, pubmed-meshheading:16029196-GTP-Binding Proteins, pubmed-meshheading:16029196-Guanosine 5'-O-(3-Thiotriphosphate), pubmed-meshheading:16029196-Humans, pubmed-meshheading:16029196-Male, pubmed-meshheading:16029196-Middle Aged, pubmed-meshheading:16029196-Neurons, pubmed-meshheading:16029196-Radioligand Assay, pubmed-meshheading:16029196-Receptors, Dopamine D2, pubmed-meshheading:16029196-Receptors, Dopamine D3, pubmed-meshheading:16029196-Sulfur Radioisotopes, pubmed-meshheading:16029196-Synaptic Transmission
pubmed:year
2005
pubmed:articleTitle
Autoradiographic mapping of dopamine-D2/D3 receptor stimulated [35S]GTPgammaS binding in the human brain.
pubmed:affiliation
Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't