Agonist high- and low-affinity states of the D2-dopamine receptor in calf brain. Partial conversion by guanine...

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.