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Identification of Dopamine “D3′’ and “D4′’ Binding Sites, Labelled with [ 3 H]2‐Amino‐6,7‐Dihydroxy‐ 1,2,3,4‐ Tetrahydronaphthalene, as High Agonist Affinity States of the D1 and D2 Dopamine Receptors, Respectively
Author(s) -
Urwyler Stephan,
Markstein Rudolf
Publication year - 1986
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1986.tb00618.x
Subject(s) - spiperone , agonist , receptor , dopamine receptor , chemistry , affinities , dopamine receptor d2 , dopamine , sch 23390 , binding site , partial agonist , stereochemistry , biology , biochemistry , endocrinology
On the basis of affinity differences for spiperone, two binding sites for [ 3 H](±)‐2‐amino‐6,7‐dihydroxy‐1,2,3,4‐tetrahydronaphthalene ([ 3 H]ADTN) in the rat brain could be distinguished: “D3′’ with a low and “D4′’ with a high affinity for spiperone. Evidence is provided that D3 and D4 sites are related to high agonist affinity states of the D1 and D2 dopamine receptors, respectively. Various well‐known selective D1 and D2 agonists and antagonists showed potencies at these sites in agreement with this hypothesis. A comparison of the B max values for [ 3 H]ADTN binding to D3 and D4 sites with the numbers of D1 receptors (labelled by [3H]SCH 23390) and of D2 receptors (labelled by [ 3 H]spiperone), both in the striatum and in the mesolimbic system, indicated that under the conditions used for 3 H‐agonist binding experiments, both populations of D1 and D2 receptors were converted to their high agonist affinity states to a considerable, although different extent. In fact, when competition experiments with [ 3 H]spiperone were performed under the conditions otherwise used for [ 3 H]ADTN binding experiments (instead of the conditions usually used for antagonist binding), substantial shifts of the displacement curves of 3,4‐dihydroxyphenylethylamine (dopamine) and ADTN toward higher affinities were observed. A comparison of the effects of various agonists and antagonists in the [3H]ADTN binding experiments and in functional tests revealed a significant correlation between their potencies at D4 binding sites and at D2 receptors modulating the release of [ 3 H]acetylcholine from striatal slices. However, in the situation of the D1/D3 pair, when the measurement of adenylate cyclase activity was taken as a functional test for D1 receptors, agonists were more active in the binding than in the functional test, whereas for many antagonists the opposite was found. The results are discussed with regard to the classification and functional aspects of brain dopamine receptors.