Persistent increase in olfactory type G-protein alpha subunit levels may underlie D1 receptor functional hypersensitivity in Parkinson disease.

ABSTRACT: Although L-dopa remains the most effective treatment of Parkinson disease, its long-term administration is hampered by the appearance of dyskinesia. Hypersensitivity of dopamine D1 receptors in the striatum has been suggested to contribute to the genesis of these delayed adverse effects. However, D1 receptor amounts are unchanged in Parkinson disease, suggesting alterations of downstream effectors. In rodents, striatal D1 receptors activate adenylyl cyclase through olfactory type G-protein alpha subunit (Galphaolf) and G-protein gamma 7 subunit (Ggamma7). We found that Galphaolf was enriched in human basal ganglia and was markedly diminished in the putamen of patients with Huntington disease, in relation with the degeneration of medium spiny neurons. In contrast, in the putamen of patients

SUBMITTER: Corvol JC 

PROVIDER: S-EPMC6729591 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature