Assessment of striatal D1 and D2 dopamine receptor-G protein coupling by agonist-induced [35S]GTP gamma S binding.
The dopamine receptor-mediated modulation of guanosine 5'-O-(gamma-[35S]thio)triphosphate ([35S]GTP gamma S) binding has been characterized in rat striatal membranes. In optimized experimental conditions, the potency of dopamine was 4.47 microM [3.02-6.61 microM] and a maximal response representing 54.8 +/- 4.5% increase above basal level was observed. Data obtained with different agonists and antagonists clearly revealed that the most important fraction of this response was reflecting D2 receptor activation. Further analysis with specific antagonists also supported evidence for the involvement of D1 dopamine receptors. The potencies of compounds interacting with D1 and D2 receptors were deduced from [35S]GTP gamma S binding experiments and compared with their binding affinities for these receptors measured in similar experimental conditions. A good correlation between these parameters was observed, supporting the applicability of this technique for the study of dopamine receptors in the central nervous system.
Geurts
M
M
Laboratoire de Pharmacologie, Université catholique de Louvain, Brussels, Belgium.
Hermans
E
E
Maloteaux
J M
JM
D000818:Animals; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D003342:Corpus Striatum / Q000378:metabolism; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013379:Substrate Specificity; D013462:Sulfur Radioisotopes
D001552:Benzazepines; D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013462:Sulfur Radioisotopes; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C067113:SK&F 81297; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs