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D2 dopamine receptors in the human brain: heterogeneity based on differences in guanine nucleotide effect on agonist binding, and their presence on corticostriatal nerve terminals

1989; Elsevier BV; Volume: 484; Issue: 1-2 Linguagem: Inglês

10.1016/0006-8993(89)90345-4

1872-6240

Jacques De Keyser, Hilde Walraevens, Jean-Paul De Backer, Guy Ebinger, Georges Vauquelin,

Neurotransmitter Receptor Influence on Behavior

In human brain, regulation of agonist binding to the D2 dopamine receptors by guanine nucleotides is different between several regions. In membranes of the anterior pituitary lobe, agonist binding is fully sensitive to GTP or Gpp(NH)p, whereas it is resistant in membranes of globus pallidus. Both guanine nucleotide-sensitive (G-S) and -insensitive (G-I) receptors are found in membranes of the striatum. The G-S and G-I type receptors display similar affinities for antipsychotic drugs of different classes, suggesting that they only differ in their effector-coupling system. We investigated the D2 receptors in striatal membranes of postmortem human brains in which corticostriatal pathways were unilaterally destroyed by an infarction. Compared to the intact side, D2 receptor densities in striata from the lesioned side were reduced by 46-65%, whereas the densities of the muscarinic cholinergic receptors, dopamine uptake sites, and D1 dopamine receptors were unchanged. In the deafferented striata all G-I, but also a substantial number of G-S receptors were lost, suggesting that both receptor subtypes are present on corticostriatal nerve terminals.