%0 Journal Article %A Jean-Christophe Corvol %A Marie-Paule Muriel %A Emmanuel Valjent %A Jean Féger %A Naïma Hanoun %A Jean-Antoine Girault %A Etienne C. Hirsch %A Denis Hervé %T Persistent Increase in Olfactory Type G-Protein α Subunit Levels May Underlie D1 Receptor Functional Hypersensitivity in Parkinson Disease %D 2004 %R 10.1523/JNEUROSCI.0676-04.2004 %J The Journal of Neuroscience %P 7007-7014 %V 24 %N 31 %X 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 α subunit (Gαolf) and G-protein γ 7 subunit (Gγ7). We found that Gαolf 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 with Parkinson disease, Gαolf and Gγ7 levels were both significantly increased. In the rat, the degeneration of dopamine neurons augmented Gαolf levels in the striatal neurons, specifically at the plasma membrane, an effect accounting for the increase of D1 response on cAMP production in dopamine-depleted striatum. In lesioned rats, Gαolf levels were normalized by a 3 week treatment with l-dopa or a D1 agonist but not with aD2-D3 agonist, supporting a Gαolf regulation by D1 receptor usage. In contrast, the increases of Gαolf levels in patients were not affected by the duration of l-dopa treatment but correlated with duration of disease. In conclusion, our results revealed in the parkinsonian putamen a prolonged elevation of Gαolf levels that may lead to a persistent D1 receptor hypersensitivity and contribute to the genesis of long-term complications of l-dopa. %U https://www.jneurosci.org/content/jneuro/24/31/7007.full.pdf