title: In human brain two subtypes of D1 dopamine receptors can be distinguished on the basis of differences in guanine nucleotide effect on agonist binding.
abstract: 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)
authors.affiliation: Department of Neurology, Akademisch Ziekenhuis, Vrije Universiteit Brussel, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: De Keyser
authors.forename: H
authors.initials: H
authors.lastname: Walraevens
authors.forename: G
authors.initials: G
authors.lastname: Ebinger
authors.forename: G
authors.initials: G
authors.lastname: Vauquelin
mesh_terms: 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
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D014316:Tritium; D006160:Guanosine Triphosphate; D004298:Dopamine