Lack of GTP-insensitive D2 dopamine receptors in Huntington's disease

Previous studies have shown that the mammalian neostriatum contains two subtypes of D2 dopamine receptors, which can be distinguished on the basis of the ability of GTP to convert high (RH) into low (RL) affinity sites for dopamine: GTP-sensitive (GS) and GTP-insensitive (GI) D2 receptors. The GI-D2 receptors in rat and human neostriatum are confined to the corticostriatal terminals. In rats, these receptors mediate the inhibitory effect of dopamine on the release of glutamate in the striatum. Here we report that the putamen in Huntington's disease (HD) lacks GI-D2 receptors. Their absence might be responsible for an inappropriate release of glutamate, which is neurotoxic in high concentrations, and might thus contribute to striatal cell death in HD.