In human brain two subtypes of D1 dopamine receptors can be distinguished on the basis of differences in guanine nucleotide effect on agonist binding.
D1 dopamine receptors were identified in membranes of human nucleus caudatus, nucleus accumbens, amygdala, and globus pallidus, by the specific binding of [3H](+)-R-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7 -ol [( 3H]SCH 23390). In these four brain regions, dopamine/[3H]SCH 23390 competition binding curves were computer-analyzed to a two-site model, distinguishing a high- (RH) and low- (RL) affinity site for dopamine. The ability of guanine nucleotides (0.4 mM GTP or 0.1 mM 5'-guanylylimidodiphosphate) to provoke a conversion of RH into RL was different between these brain regions. In amygdala, a complete conversion was seen, whereas there was no guanine nucleotide-effect on RH in globus pallidus. In nucleus caudatus and nucleus accumbens, guanine nucleotides provoked only a partial conversion of RH into RL, suggesting that these brain regions may contain guanine nucleotide-sensitive and -insensitive receptors. Heating of the membranes at 60 degrees C for 5 min had the same effect as guanine nucleotides. The pharmacological profiles of the guanine nucleotide-sensitive and -insensitive D1 receptors were similar, suggesting that D1 receptors in human brain are heterogeneous only with respect to their effector-coupling mechanism: guanine nucleotide-sensitive receptors, which are capable of undergoing functional coupling with Gs, and guanine nucleotide-insensitive receptors, which are not.(ABSTRACT TRUNCATED AT 250 WORDS)
De Keyser
J
J
Department of Neurology, Akademisch Ziekenhuis, Vrije Universiteit Brussel, Belgium.
Walraevens
H
H
Ebinger
G
G
Vauquelin
G
G
D000368:Aged; D000369:Aged, 80 and over; D000679:Amygdala / Q000378:metabolism; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D002544:Cerebral Infarction / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists; D005260:Female; D005917:Globus Pallidus / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000378:metabolism; D009928:Organ Specificity; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D012016:Reference Values; D014316:Tritium
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D014316:Tritium; D006160:Guanosine Triphosphate; D004298:Dopamine