AGONIST HIGH-AFFINITY AND LOW-AFFINITY STATES OF THE D2-DOPAMINE RECEPTOR IN CALF BRAIN - PARTIAL CONVERSION BY GUANINE-NUCLEOTIDE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 25  (1) , 10-17
Abstract
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 the agonist low-affinity state, the effect of a guanine nucleotide [Gpp(NH)p] was examined on the competition between [3H]spiperone and dopamine agonists for binding to homogenates of calf caudate nucleus. [3H]spiperone labeled sites had different affinities for agonists as well as antagonists [(+)-butaclamol, (-)-apomorphine, (-)sulpiride, bromocriptine, R43448, (1-(4-fluorophenylmethyl)-N-(1-[2-(2-pyridinyl)ethyl]-4-piperidinyl)-1H-benzimidazol-2-amine). (.+-.) LY156258 and ADTN (2-amino-6,7-dihydroxytetrahydronaphthalene)]. Agonists recognized 3 components of [3H]spiperone binding. Two of these components were related to the D2-dopaminergic receptor. These 2 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.

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