Gpp(NH)p stimulates [3H]raclopride binding to homogenates from human putamen and accumbens

The effects of the stable GTP analogue Gpp(NH)p (5'-guanylyl imido diphosphate) were examined on in vitro [3H]raclopride binding to dopamine D2 receptors in preparations from post mortem human brains. The estimated number of receptors in the brain was 29% and 38% higher in putamen and accumbens, respectively, when determined in the presence of Gpp(NH)p as compared to its absence. The interaction of agonists was biphasic confirming the two affinity state model of the receptor--G-protein complex. The addition of Gpp(NH)p to the assay abolished the two site competition of apomorphine with [3H]raclopride binding in both regions studied. The non-specific binding at high concentrations of apomorphine was not significantly affected by the addition of Gpp(NH)p, indicating that only the specific binding of [3H]raclopride to the dopamine D2 receptor is increased.