Coupling of D1 dopamine receptors to the guanine nucleotide binding protein Gs is deficient in Huntington's disease.
Human brain contains two subtypes of D1 dopamine receptors, which both exist under high- (RH) and low-agonist affinity (RL) sites, but can be distinguished on the basis of the ability of GTP to convert RH into RL. The amygdala contains exclusively GTP-sensitive (GS) D1 receptors, frontal cortex exclusively GTP-insensitive (GI) D1 receptors, and putamen both GS and GI receptors. In contrast with controls, we were unable to detect RH sites in amygdala from patients with Huntington disease (HD). The amount of RH sites in normal and HD frontal cortex were similar. In putamen, the GTP-induced partial conversion of RH into RL, observed in controls, was absent in HD. The results suggest that coupling of GS-D1 receptors with the guanine nucleotide binding protein Gs may be deficient in HD.
De Keyser
J
J
Department of Neurology, Academisch Ziekenhuis, Vrije Universiteit Brussel, Belgium.
De Backer
J P
JP
Ebinger
G
G
Vauquelin
G
G
D000328:Adult; D000368:Aged; D000679:Amygdala / Q000378:metabolism*; D001552:Benzazepines / Q000378:metabolism; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D012559:Schizophrenia / Q000378:metabolism
D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D019204:GTP-Binding Proteins