Agonist high- and low-affinity states of the D2-dopamine receptor in calf brain. Partial conversion by guanine nucleotide.
In order to determine whether D2-dopaminergic receptors in brain exist in different affinity states for agonists and whether these receptors could be completely converted from their agonist high-affinity state to their agonist low-affinity state, we examined the effect of a guanine nucleotide on the competition between [3H]spiperone and dopamine agonists for binding to homogenates of calf caudate nucleus. [3H]spiperone labeled sites having different affinities for agonists as well as antagonists. Agonists recognized three components of [3H]spiperone binding. Two of these components were related to the D2-dopaminergic receptor. These two sites appeared to represent interconvertible states, each having different affinities for agonists. This was supported by the observation of an apparent guanine nucleotide-induced "conversion" of sites with high affinity to those having low affinity for the agonist. This effect of the guanine nucleotide was incomplete, such that a significant proportion of the high-affinity sites (21%) remained in the presence of an excess of the nucleotide. These high-affinity, guanine nucleotide-insensitive sites may represent a distinct class of binding sites having high affinity for both agonists and antagonists or may be the result at equilibrium of an agonist-independent interaction of the receptor and the guanine nucleotide.
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002421:Caudate Nucleus / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007700:Kinetics; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D006165:Guanylyl Imidodiphosphate; D013134:Spiperone; C011639:ADTN